Hubbry Logo
Targeted therapyTargeted therapyMain
Open search
Targeted therapy
Community hub
Targeted therapy
logo
8 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Targeted therapy
Targeted therapy
Targeted therapy
View on Wikipedia
from Wikipedia
Patients and their diseases are profiled in order to identify the most effective treatment for their specific case.

Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer,[1] others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth,[2] rather than by simply interfering with all rapidly dividing cells (e.g. with traditional chemotherapy). Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy (and thus distinguished from chemotherapy, that is, cytotoxic therapy). However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.

Another form of targeted therapy involves the use of nanoengineered enzymes to bind to a tumor cell such that the body's natural cell degradation process can digest the cell, effectively eliminating it from the body.

Targeted cancer therapies are expected to be more effective than older forms of treatments and less harmful to normal cells. Many targeted therapies are examples of immunotherapy (using immune mechanisms for therapeutic goals) developed by the field of cancer immunology. Thus, as immunomodulators, they are one type of biological response modifiers.

The most successful targeted therapies are chemical entities that target or preferentially target a protein or enzyme that carries a mutation or other genetic alteration that is specific to cancer cells and not found in normal host tissue.[3] One of the most successful molecular targeted therapeutics is imatinib, marketed as Gleevec, which is a kinase inhibitor with exceptional affinity for the oncofusion protein BCR-Abl which is a strong driver of tumorigenesis in chronic myelogenous leukemia. Although employed in other indications, imatinib is most effective targeting BCR-Abl. Other examples of molecular targeted therapeutics targeting mutated oncogenes, include PLX27892 which targets mutant B-raf in melanoma.

There are targeted therapies for lung cancer, colorectal cancer, head and neck cancer, breast cancer, multiple myeloma, lymphoma, prostate cancer, melanoma and other cancers.[1][4][5]

Biomarkers are usually required to aid the selection of patients who will likely respond to a given targeted therapy.[6]

Co-targeted therapy involves the use of one or more therapeutics aimed at multiple targets, for example PI3K and MEK, in an attempt to generate a synergistic response[5] and prevent the development of drug resistance.[7][8]

The definitive experiments that showed that targeted therapy would reverse the malignant phenotype of tumor cells involved treating Her2/neu transformed cells with monoclonal antibodies in vitro and in vivo by Mark Greene's laboratory and reported from 1985.[9]

Some have challenged the use of the term, stating that drugs usually associated with the term are insufficiently selective.[10] The phrase occasionally appears in scare quotes: "targeted therapy".[11] Targeted therapies may also be described as "chemotherapy" or "non-cytotoxic chemotherapy", as "chemotherapy" strictly means only "treatment by chemicals". But in typical medical and general usage "chemotherapy" is now mostly used specifically for "traditional" cytotoxic chemotherapy.

Types

[edit]

The main categories of targeted therapy are currently small molecules and monoclonal antibodies.

Small molecules

[edit]
Mechanism of imatinib

Many are tyrosine-kinase inhibitors.

Small molecule drug conjugates

[edit]
  • Vintafolide is a small molecule drug conjugate consisting of a small molecule targeting the folate receptor. It is currently in clinical trials for platinum-resistant ovarian cancer (PROCEED trial) and a Phase 2b study (TARGET trial) in non-small-cell lung carcinoma (NSCLC).[22]

Serine/threonine kinase inhibitors (small molecules)

[edit]
See also: Serine/threonine kinase

Monoclonal antibodies

[edit]
Main article: Monoclonal antibody therapy

Several are in development and a few have been licensed by the FDA and the European Commission. Examples of licensed monoclonal antibodies include:

Many antibody-drug conjugates (ADCs) are being developed. See also antibody-directed enzyme prodrug therapy (ADEPT).

Progress and future

[edit]

In the U.S., the National Cancer Institute's Molecular Targets Development Program (MTDP) aims to identify and evaluate molecular targets that may be candidates for drug development. A systematic review published in Cochrane database found that targeted therapies significantly improve progression-free survival by 35 to 40% in metastatic or relapsed cancer. While the research points to promising clinical outcomes, there is still limited evidence on the long-term effects of targeted therapies in terms of overall survival, quality of life, and severe adverse events. [30]

See also

[edit]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Targeted therapy

View on Grokipedia
from Grokipedia
Targeted therapy, also known as molecularly targeted therapy, is a type of medical treatment that uses drugs or other substances to target specific molecules, such as proteins or genes, involved in processes, particularly within cancer cells that drive their growth, division, and spread, while aiming to spare healthy cells. While most commonly associated with , targeted therapies are also used in non-oncologic conditions such as autoimmune and inflammatory s. Developed as a cornerstone of precision medicine, it relies on identifying genetic or molecular changes unique to the diseased tissue through testing, allowing for personalized treatment approaches. First conceptualized in the late by as a "magic bullet" for selective targeting, targeted therapies emerged clinically in the late 20th century with approvals like in 1998 for HER2-positive and in 2001 for (CML). These therapies work by interfering with key cellular processes in target cells, such as blocking growth signals, inhibiting blood vessel formation to starve tumors (anti-angiogenesis), triggering cell death (apoptosis), or delivering toxins directly to diseased cells. The two primary categories are small-molecule drugs, which are pills or liquids that enter cells to disable intracellular targets like enzymes, and monoclonal antibodies, which are laboratory-made proteins administered intravenously to bind to surface proteins on target cells. Hormone therapies, a subset, block or lower hormones that fuel certain hormone-sensitive conditions like breast or prostate cancers. Common targets include mutated genes or overexpressed proteins such as EGFR, HER2, BRAF, and KRAS, which are tested via biopsies to determine eligibility. Compared to traditional , which indiscriminately kills fast-dividing cells and often causes widespread side effects like and , targeted therapies offer greater precision and typically fewer severe adverse effects, though they can still cause issues like skin rashes, , , or liver problems depending on the drug. They are administered in various settings—pills at home or infusions in clinics—and may be used alone, before to shrink tumors, or combined with , , or to enhance outcomes. Approved for numerous cancers including , , colorectal, and , targeted therapies have revolutionized treatment for biomarker-positive cases, with ongoing addressing resistance mechanisms through combination strategies and next-generation inhibitors.

Fundamentals

Definition and Principles

Targeted therapy represents a form of that employs agents designed to interact with specific molecular implicated in progression, particularly in cancer, thereby distinguishing it from non-specific treatments that affect both diseased and healthy cells indiscriminately. These therapies function as precision interventions, focusing on aberrant cellular components such as mutated proteins or dysregulated signaling pathways to disrupt cancer cell survival and growth while sparing normal tissues. At its core, targeted therapy operates on the principle of selectivity, aiming to inhibit or modulate specific molecular entities like oncogenes, tumor suppressor genes, or signaling cascades—such as the PI3K/AKT/ pathway—that drive oncogenesis. This approach emphasizes the use of biomarkers, including genetic mutations or protein expressions, to stratify patients and predict therapeutic response, enabling personalized treatment selection that maximizes efficacy and minimizes off-target effects. By exploiting the molecular differences between cancer and normal cells, these therapies achieve a higher compared to traditional cytotoxic agents. The basic workflow of targeted therapy begins with the identification of a validated molecular target through genomic, proteomic, or functional analyses of diseased tissues. Subsequent involves developing agents, such as small molecules or biologics, that bind to or inhibit the target, leading to therapeutic effects like induction of in cancer cells or blockade of uncontrolled proliferation. For instance, exemplifies this process by targeting a specific in chronic myeloid leukemia, illustrating the precision of such interventions. This paradigm draws inspiration from Paul Ehrlich's early 20th-century "magic bullet" concept, which envisioned therapeutic agents that precisely strike pathological targets without , a foundational idea in modern that underscores targeted therapy's departure from broad .

Comparison to Conventional Therapies

Targeted therapy differs fundamentally from conventional in its and impact on healthy tissues. While indiscriminately targets rapidly dividing cells by interfering with and , leading to widespread systemic such as , , and myelosuppression, targeted therapy selectively inhibits specific molecular drivers of cancer, such as mutated proteins or signaling pathways, thereby minimizing damage to normal cells. This precision results in a more favorable profile for targeted therapies, with reduced rates of severe myelosuppression and other chemotherapy-associated adverse effects, although they can still cause unique side effects like skin rashes or cardiovascular issues depending on the agent. In terms of efficacy, targeted therapies often achieve higher objective response rates in biomarker-selected patients—for instance, up to 70-80% in EGFR-mutated non-small cell —compared to the 20-40% typically seen with standard regimens in unselected populations, enabling better personalization through genomic testing. In contrast to , which delivers localized high-energy rays to destroy cancer cells in a specific area and is limited by tissue-specific risks like or secondary malignancies, targeted therapy provides systemic treatment that can address widespread or metastatic more effectively without the constraints of anatomical targeting. excels in curative intent for localized tumors but offers primarily palliative benefits for metastases, whereas targeted agents circulate throughout the body to inhibit tumor progression at multiple sites, often with lower risks of radiation-induced toxicities in non-irradiated tissues. Targeted therapy also contrasts with immunotherapy, which harnesses the patient's immune system to recognize and attack cancer cells through mechanisms like checkpoint inhibition, rather than directly blocking tumor-specific drivers such as mutant kinases. While both approaches are systemic and personalized, targeted therapy yields rapid responses in tumors harboring actionable alterations but may face resistance over time, whereas immunotherapy can produce durable remissions yet with variable response rates across patients. Hormonal therapy, a subset of targeted approaches, specifically modulates hormone receptors like estrogen to starve receptor-positive cancers, differing from the broader scope of targeted therapies that address diverse genetic and molecular alterations beyond hormonal pathways. Overall, these distinctions underscore targeted therapy's role in precision oncology, particularly for advanced disease, with improved tolerability and efficacy in molecularly defined subsets compared to broader conventional modalities.

History

Early Discoveries

The foundational insights into targeted therapy emerged in the mid-20th century through discoveries establishing the molecular basis of cancer, particularly the identification of oncogenes and tumor suppressor genes. In the 1950s and 1960s, research on retroviruses like the (RSV) laid early groundwork, with Peyton Rous's 1911 discovery of a transmissible sarcoma in chickens later recognized as viral-induced oncogenesis. By 1970, isolated a temperature-sensitive of RSV, revealing the viral src as a key driver of cellular transformation, marking the first identification of a specific oncogene. This work, expanded by J. Michael Bishop and in the 1970s, demonstrated that oncogenes are mutated versions of normal cellular proto-oncogenes involved in growth regulation, shifting toward molecular targets. Concurrently, Alfred Knudson's 1971 proposed tumor suppressor genes, where both alleles must be inactivated for tumorigenesis, as evidenced by studies; this concept was later validated in the 1980s through genetic analyses, such as 1983 studies showing in tumors, with molecular identification of loss-of-function mutations in tumor suppressor genes like RB1 following in 1986. A pivotal technological advance came in 1975 with Georges J.F. Köhler and César Milstein's development of the , which fused antibody-producing B cells with myeloma cells to generate immortalized cell lines secreting identical monoclonal antibodies. This method, awarded the in or in 1984, enabled the production of highly specific antibodies against molecular targets, revolutionizing the potential for precise therapeutic interventions in cancer and other diseases. By providing tools to target specific proteins on cell surfaces or in signaling pathways, bridged and therapeutic application, influencing subsequent antibody-based targeting strategies. In the late and , research on protein kinases illuminated their role as central hubs in signaling, particularly kinases. Tony Hunter and others identified as a key regulatory mechanism in 1979, with studies showing that the src oncogene product exhibited activity. By 1980, experiments on the (EGFR) demonstrated that binding induced , establishing EGFR as a proto-oncogene activated in various cancers and a prime target for inhibition. These findings underscored how aberrant kinase signaling drives uncontrolled proliferation, setting the stage for kinase-targeted therapies. Pre-clinical validation of target inhibition relied on cell lines and animal models during the 1980s, with HER2 (human epidermal growth factor receptor 2) serving as a representative example in . Initially identified as the neu oncogene in neuroglioblastomas in , HER2 was linked to human breast tumors through studies showing in approximately 30% of cases, promoting aggressive growth in model systems. Experiments in cell lines and xenograft models confirmed that HER2 overexpression enhanced tumorigenicity, while blockade reduced proliferation, validating molecular targeting in controlled settings. The era also witnessed a paradigm shift from empirical drug discovery to rational design, propelled by advances in structural biology such as X-ray crystallography. Pioneered in the 1950s with the structure of myoglobin, crystallographic techniques by the 1970s and 1980s allowed visualization of protein active sites, enabling the design of molecules to fit specific targets like kinases. This approach, exemplified by early inhibitor modeling against enzyme structures, facilitated precise modulation of disease-related proteins, laying the groundwork for structure-guided targeted therapies.

Major Milestones

The development of targeted therapies accelerated in the with the preclinical synthesis of STI571 (later ), the first small-molecule designed to specifically target the BCR-ABL in chronic myeloid leukemia (CML). This compound, identified through by researchers, demonstrated potent inhibition of BCR-ABL kinase activity in cell lines and animal models, laying the groundwork for precision oncology by linking oncogenic drivers to therapeutic intervention. The late 1990s marked the entry of monoclonal antibodies into clinical practice, with rituximab receiving FDA approval on November 26, 1997, as the first targeted therapy for patients with relapsed or refractory low-grade or follicular CD20-positive B-cell . This chimeric antibody revolutionized treatment by selectively depleting malignant B cells via and complement activation. Shortly thereafter, (Herceptin) was approved by the FDA in September 1998 for HER2-overexpressing , establishing HER2 as a viable target and improving response rates when combined with . A pivotal regulatory milestone occurred in 2001 with the FDA approval of (Gleevec) on May 10 for newly diagnosed chromosome-positive CML in chronic phase, representing the first targeted therapy to transform a fatal disease into a manageable . Clinical trials showed complete cytogenetic responses in over 80% of patients, dramatically reducing progression to . The 2010s saw expansions into novel modalities, including BRAF inhibitors and antibody-drug conjugates (ADCs). Vemurafenib (Zelboraf) gained FDA approval on August 17, 2011, for unresectable or metastatic melanoma harboring BRAF V600E mutations, achieving objective response rates of approximately 50% in pivotal trials and validating mutant kinase targeting in solid tumors. In 2013, ado-trastuzumab emtansine (Kadcyla) was approved on February 22 for HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane, introducing ADCs that deliver cytotoxic payloads selectively to tumor cells and extending progression-free survival by several months. Entering the 2020s, breakthroughs addressed previously "undruggable" targets, exemplified by the FDA's accelerated approval of (Lumakras) on May 28, 2021, for G12C-mutated non-small cell after prior , with response rates around 37% in the CodeBreaK 100 trial. Bispecific antibodies also proliferated, with approvals such as (Lunsumio) in December 2022 for relapsed or refractory and (Tecvayli) in October 2022 for relapsed or refractory , enabling T-cell redirection against tumor antigens and achieving complete response rates exceeding 30% in heavily pretreated patients. In 2023-2025, further innovations included FDA approval of repotrectinib in November 2023 for ROS1-positive non-small cell and NTRK fusion-positive solid tumors, and tarlatamab in May 2024 as the first bispecific T-cell engager for extensive-stage . By 2025, combinations of targeted therapies with immunotherapies had become standard in several cancers, such as BRAF/MEK inhibitors plus PD-1 blockers in , enhancing durable responses through synergistic immune activation. These milestones have profoundly impacted global cancer outcomes, particularly in CML, where imatinib drove a more than 50% improvement in long-term —from historical 5-year rates below 50% to over 90% in the imatinib era—shifting the paradigm from palliative to curative potential in many cases.

Molecular Targets

Types of Targets

Targeted therapies focus on specific molecular entities that play critical roles in , particularly in cancer, by disrupting aberrant signaling, proliferation, or mechanisms. These are typically proteins or nucleic acids that are dysregulated due to genetic alterations, overexpression, or , enabling selective intervention with minimal off-target effects compared to traditional chemotherapies. The primary categories include kinases, receptors, intracellular proteins, cell surface markers, and emerging non-protein , each contributing uniquely to pathological processes like uncontrolled cell growth and . Recent advancements as of 2025 include protein degraders like PROTACs targeting undruggable proteins such as mutants, expanding options for previously challenging . Kinases are enzymes that catalyze the transfer of phosphate groups to proteins, thereby regulating key signaling pathways essential for cell proliferation, differentiation, and survival; their dysregulation, often through mutations or amplification, drives oncogenesis in various cancers. Tyrosine kinases, such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), are receptor or non-receptor proteins that phosphorylate tyrosine residues, activating downstream cascades like MAPK/ERK and PI3K/AKT that promote tumor growth and invasion, particularly in non-small cell lung cancer (NSCLC). Serine/threonine kinases, including BRAF and mitogen-activated protein kinase kinase (MEK), function within the RAS/RAF/MAPK pathway to relay signals for cell cycle progression and anti-apoptotic responses; mutations in BRAF, for instance, occur in 50-70% of melanomas, leading to constitutive pathway activation and resistance to apoptosis. Growth factor receptors are transmembrane proteins that bind ligands to initiate intracellular signaling for and vascularization; their overexpression or amplification in tumors sustains autocrine and paracrine loops that fuel pathogenesis. Human 2 (HER2), for example, dimerizes to activate PI3K/AKT and MAPK pathways, enhancing proliferation and survival in approximately 20-25% of cancers. receptor (VEGFR) binds VEGF to stimulate endothelial and tube formation, thereby promoting and tumor in solid tumors like colorectal and renal cancers. Intracellular proteins encompass a diverse group of non-receptor molecules located within the cell that orchestrate metabolic, transcriptional, or signaling functions; alterations in these proteins disrupt and enable oncogenic transformation. Fusion proteins like BCR-ABL, resulting from chromosomal translocations, exhibit constitutive activity that hyperactivates signaling pathways, driving uncontrolled proliferation in chronic myeloid leukemia (CML). Mutant enzymes such as 1 and 2 (IDH1/2) produce oncometabolite 2-hydroxyglutarate, which inhibits epigenetic regulators and promotes gliomagenesis by altering patterns. Epigenetic modifiers including histone deacetylases (HDACs) remove acetyl groups from s, leading to condensation and repression of tumor suppressor genes, thereby facilitating survival and resistance to stress in hematologic and solid malignancies; recent approvals as of 2025 include next-generation inhibitors for and solid tumors. Cell surface markers are antigens expressed on the plasma of malignant cells, often uniquely or overexpressed compared to normal tissues, allowing for precise recognition and elimination of diseased cells. , a B-cell-specific , regulates calcium influx and cell ; its expression on mature B-lymphocytes makes it a hallmark of B-cell lymphomas and leukemias, where it supports pathogenic clonal expansion. , a type II transmembrane , facilitates metabolism and ; its upregulation in cells correlates with tumor progression and , providing a selective marker for advanced disease. Emerging non-protein targets represent novel classes beyond traditional proteins, including nucleic acids and metabolic components that influence gene expression or repair mechanisms critical to cancer pathogenesis, as well as degraders for protein targets. MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate oncogenes and tumor suppressors; dysregulated miRNAs, such as miR-21, promote proliferation and invasion by silencing apoptosis-related genes in multiple cancers. Metabolic enzymes like poly(ADP-ribose) polymerase (PARP) catalyze ADP-ribosylation to facilitate DNA repair; in BRCA-mutated tumors, PARP dependency creates synthetic lethality, where inhibition exploits defective homologous recombination and leads to genomic instability.

Identification and Validation Methods

Identification and validation of molecular in targeted therapy involve a multifaceted approach combining high-throughput genomic and proteomic technologies, functional assays, and computational modeling to pinpoint and confirm therapeutically actionable alterations in diseases, particularly cancer. These methods ensure that are not only associated with disease pathology but also amenable to pharmacological intervention, minimizing off-target effects and enhancing therapeutic precision. Seminal efforts, such as those from large-scale consortia, have established standardized pipelines for target discovery, while advancements in single-cell and spatial further refine validation by capturing heterogeneity within tumors. Genomic methods form the cornerstone of target identification by systematically cataloging genetic alterations that drive disease progression. Next-generation sequencing (NGS) enables the detection of somatic mutations, copy number variations, and structural rearrangements across tumor genomes, facilitating the prioritization of driver genes over passenger mutations. For instance, (TCGA) project, which analyzed over 11,000 tumors from 33 cancer types, identified hundreds of recurrently mutated driver genes, such as EGFR in lung adenocarcinoma and BRAF in , providing a foundational resource for targeted therapies. Functional validation of these candidates often employs CRISPR-Cas9-based genome-wide screens, which introduce targeted knockouts or perturbations to assess gene essentiality in disease models. These screens have uncovered context-specific dependencies, such as synthetic lethal interactions in BRCA-mutated cancers, confirming targets like for therapeutic exploitation. Proteomic approaches complement by directly profiling protein expression, modifications, and interactions, revealing post-translational dysregulation that NGS alone cannot capture. (MS)-based proteomics quantifies thousands of proteins simultaneously, identifying overexpressed oncoproteins or altered signaling hubs in patient samples. , a specialized variant, maps events to delineate activated pathways, such as PI3K/AKT signaling in HER2-positive breast cancers, which informs inhibitor selection. These techniques have been pivotal in validating targets like mutant KRAS, where hyper patterns correlate with therapeutic vulnerabilities. By integrating with , enhances target specificity, as demonstrated in studies profiling drug-resistant tumors to uncover adaptive resistance mechanisms. Pre-clinical validation bridges discovery to therapeutic application through experimental models that test target engagement and downstream effects. In vitro assays, including kinase activity screens and cell viability readouts, evaluate target inhibition using small-molecule probes or siRNA, confirming pharmacological tractability for enzymes like kinases, which constitute over 30% of approved . Xenograft models, where human tumor cells are implanted into immunocompromised mice, assess efficacy and , replicating interactions to validate such as VEGF in angiogenesis-driven cancers. Patient-derived organoids (PDOs), three-dimensional cultures retaining tumor heterogeneity and genetic fidelity, offer a more physiologically relevant platform; for example, PDOs from colorectal cancers have validated EGFR inhibitors by mirroring patient responses, with success rates exceeding 80% concordance in predictive screenings. These models collectively reduce attrition in by prioritizing with robust anti-tumor activity. Biomarker correlation links identified targets to clinical outcomes, ensuring their relevance for patient stratification. Techniques like (FISH) detect gene amplifications, such as HER2 in , where ratios exceeding 2.0 copies per cell predict responsiveness to , with response rates up to 34% in amplified cases versus lower in non-amplified tumors. Associating with survival data—via cohorts showing HER2 amplification correlating with poorer yet improved therapy outcomes—validates targets by establishing prognostic and predictive value. This step is crucial for regulatory approval, as seen in guidelines requiring biomarker assays for targeted agents. Computational tools accelerate target prioritization by predicting druggability and structural feasibility, particularly through AI-driven analyses post-2020. AlphaFold 2, released in 2021, predicts protein structures with near-atomic accuracy for over 200 million proteins, enabling virtual screening of binding pockets and inhibitor design, transforming "undruggable" targets like RAS into viable candidates by modeling conformational dynamics. As of 2025, AlphaFold 3 (released May 2024) extends this to predict interactions with ligands, DNA, RNA, and modified residues, further aiding complex target validation and drug discovery. Machine learning algorithms integrate multi-omics data to score targets based on expression, mutation frequency, and pathway centrality, as in platforms forecasting therapeutic windows with 70-90% accuracy in retrospective validations. These tools, combined with molecular dynamics simulations, streamline validation by identifying high-confidence targets before wet-lab confirmation, significantly shortening discovery timelines.

Therapeutic Modalities

Small-Molecule Inhibitors

Small-molecule inhibitors represent a cornerstone of targeted therapy, consisting of low-molecular-weight compounds (typically under 500 Da) that can readily diffuse across cell membranes to engage intracellular targets such as kinases and s. These agents are primarily designed for , leveraging favorable pharmacokinetic properties like high and suitable absorption, distribution, , and profiles to achieve therapeutic concentrations in tissues. Design strategies often focus on ATP-competitive binding, where the inhibitor occupies the ATP-binding pocket of the target , forming key hydrogen bonds with the hinge region to block and downstream signaling; alternatively, allosteric binding modulates conformation without directly competing with ATP, enhancing selectivity. A prominent class includes inhibitors (TKIs), which target receptor and non-receptor s to disrupt oncogenic signaling pathways. , the first approved TKI, competitively inhibits the BCR-ABL fusion kinase in chronic myeloid leukemia by binding the inactive conformation with an in the nanomolar range, leading to blockade of the PI3K/AKT and MAPK pathways and induction of in malignant cells. Similarly, targets mutant EGFR in non-small cell lung cancer, reversibly binding the ATP site ( approximately 2 nM for EGFR) to halt cell proliferation through RAS/RAF/MEK/ERK pathway inhibition. In , BRAF/MEK inhibitors like and exemplify targeted efficacy; selectively inhibits BRAFV600E ( ~30 nM), while combination with trametinib (a ) amplifies pathway suppression, resulting in tumor regression via arrest at . Serine/threonine kinase inhibitors further expand this modality, addressing diverse targets beyond tyrosine phosphorylation. Sorafenib, a multi-kinase inhibitor, binds ATP-competitively to RAF kinases and receptors ( ~6 nM for RAF), thereby inhibiting and tumor cell survival through dual blockade of MAPK and PI3K pathways, often culminating in cytostatic effects like reduced proliferation. Palbociclib, a selective CDK4/6 inhibitor, exemplifies precision in regulation; it allosterically binds CDK4/6 ( ~11 nM for CDK4), preventing and enforcing G1 arrest to suppress Rb-positive tumor growth. These mechanisms underscore how small-molecule inhibitors achieve therapeutic outcomes by precisely interrupting hyperactive signaling cascades essential for cancer cell maintenance. Despite their advantages, developing small-molecule inhibitors poses significant challenges, particularly in achieving specificity to minimize off-target effects that can lead to . For instance, many TKIs exhibit polypharmacology, inhibiting unintended kinases and causing adverse events such as or gastrointestinal issues due to VEGFR . remains a critical concern, with agents like linked to vascular occlusion and through disruption of pro-survival pathways in cardiomyocytes, highlighting the need for rigorous selectivity profiling during . Ongoing efforts emphasize structure-based optimization to enhance on-target potency while reducing such risks.

Biologic Agents

Biologic agents, particularly monoclonal antibodies (mAbs), represent a cornerstone of targeted therapy by leveraging large-molecule structures to precisely engage extracellular or cell surface targets such as receptors, thereby modulating disease processes without cellular internalization. These agents primarily function through mechanisms including receptor blockade, which inhibits binding and downstream signaling; immune effector functions like (ADCC), where the antibody's Fc region recruits natural killer cells to lyse target cells; and (CDC), involving activation of the complement cascade to form membrane attack complexes. Additionally, some mAbs disrupt signaling pathways by inducing receptor internalization or conformational changes, leading to attenuated or survival signals. Naked mAbs, which are unmodified antibodies, exemplify these principles in clinical use. For instance, targets the HER2 receptor on cells, blocking its dimerization and signaling while promoting ADCC to eliminate HER2-overexpressing tumor cells. Similarly, rituximab binds on B-cell lymphomas, primarily inducing ADCC and CDC to deplete malignant B cells through immune-mediated destruction. Another key example is , an mAb that neutralizes , thereby inhibiting and starving tumors of essential blood supply in various cancers. Bispecific antibodies extend this paradigm by simultaneously binding two distinct antigens, often bridging tumor cells and immune effectors for enhanced . Blinatumomab, a /CD3 bispecific T-cell engager, redirects cytotoxic T cells to -positive cells by engaging CD3 on T cells, forming an that triggers perforin-mediated tumor . Production of these biologic agents relies on technology, where genes encoding the antibody are inserted into Chinese hamster ovary (CHO) cells for high-yield expression and secretion. To minimize immunogenicity in humans, murine-derived antibodies undergo humanization, grafting complementarity-determining regions onto human antibody frameworks, which reduces anti-drug antibody responses while preserving binding affinity.

Conjugates and Emerging Modalities

Antibody-drug conjugates (ADCs) represent a sophisticated class of targeted therapies that integrate a (mAb) with a cytotoxic through a chemical linker, enabling precise delivery of potent drugs to cancer cells expressing specific s. The mAb binds to the target on the cell surface, facilitating , after which the linker releases the cytotoxin intracellularly to induce . A prominent example is (T-DM1), where the humanized mAb targets HER2-positive cells and is conjugated via a non-cleavable thioether linker to emtansine, a maytansinoid that disrupts assembly. In heterogeneous tumors, ADCs can exhibit a , particularly with cleavable linkers and membrane-permeable payloads, allowing the released cytotoxin to diffuse and kill adjacent antigen-negative cells. Small-molecule drug conjugates (SMDCs) extend this targeted delivery paradigm using bispecific small molecules as ligands, offering advantages in synthesis simplicity and tissue penetration over larger antibody-based systems. Typically comprising a small-molecule targeting moiety, a cleavable linker, and a cytotoxic , SMDCs selectively accumulate in tumor tissues via ligand-receptor interactions, releasing the locally to minimize off-target toxicity. For instance, VIP236 employs an αvβ3 integrin-binding small molecule to direct a topoisomerase I inhibitor to angiogenic tumor vasculature, demonstrating enhanced efficacy in preclinical models of tumors. This format is particularly suited for targets inaccessible to antibodies, with ongoing developments focusing on fibroblast activation protein (FAP) in the . Other conjugate modalities include radioligands and proteolysis-targeting chimeras (PROTACs), which leverage radioactive or degradative payloads for amplified therapeutic impact. Radioligand therapies, such as lutetium-177-PSMA-617 (Pluvicto), target prostate-specific membrane antigen (PSMA) overexpressed on cells, delivering β-emitting radionuclides to induce DNA damage and while sparing healthy tissues. Approved for PSMA-positive metastatic castration-resistant , this approach has shown significant declines in over 50% of patients in clinical studies. PROTACs, meanwhile, are heterobifunctional small molecules that recruit ubiquitin ligases to target proteins, promoting their ubiquitination and proteasomal degradation rather than mere inhibition. This event-driven mechanism addresses "undruggable" targets in , with preclinical PROTACs degrading oncoproteins like BCR-ABL in hematological malignancies. Emerging modalities build on these foundations to further refine targeting and delivery, including cell-penetrating peptides (CPPs), nanobodies, and gene-editing integrations. CPPs, short amphipathic sequences that facilitate transmembrane transport, enhance the intracellular delivery of conjugated therapeutics, such as chemotherapeutic agents or immunotherapies, to tumor cells with improved endosomal escape and selectivity. In cancer applications, CPPs have been conjugated to payloads for targeted tumor immunotherapy, showing promise in preclinical models by boosting antigen presentation and T-cell infiltration. Nanobodies, single-domain antibody fragments derived from camelid heavy-chain antibodies, offer compact alternatives for conjugate targeting due to their high stability, tissue penetration, and ease of engineering into bispecific formats. They have been integrated into drug delivery systems for precise tumor homing, such as CD155-targeted nanobodies delivering payloads to lung adenocarcinoma cells in recent studies. In early clinical stages as of 2025, CRISPR-based targeting modalities are being evaluated in trials, where Cas9 ribonucleoproteins are delivered via targeted vectors to edit disease-causing mutations in specific cell types, such as in CRISPR-edited T cells for colorectal cancer, aiming for durable therapeutic effects. These conjugates and emerging formats enhance potency through amplification, concentrating high-impact agents at sites to overcome limitations of unbound therapies while reducing systemic exposure.

Clinical Applications

In

Targeted therapy has revolutionized by enabling precise interventions against molecular drivers in various cancers, leading to improved survival rates and reduced reliance on broad-spectrum in select populations. In solid tumors, HER2-targeted agents such as and are approved for HER2-positive , where dual antibody therapy combined with achieves survival rates exceeding 90% in early-stage . For metastatic HER2-positive , these therapies, including antibody-drug conjugates like , have extended median overall survival to over 4 years in pretreated . In non-small cell lung cancer (NSCLC), EGFR inhibitors (TKIs) like yield objective response rates (ORR) of 70-80% in EGFR-mutant as first-line treatment, with median (PFS) of 18-19 months. Similarly, such as demonstrate ORR of 60-72% in ALK-positive NSCLC, particularly in the frontline setting, outperforming earlier agents like . In , anti-EGFR monoclonal antibodies like and are approved for RAS wild-type metastatic following KRAS/NRAS testing, improving PFS by approximately 2-3 months when added to in eligible . Hematologic malignancies represent a cornerstone of targeted therapy success, with dramatic outcomes in chronic myeloid leukemia (CML) from BCR-ABL inhibitors. , the first approved TKI for newly diagnosed chronic-phase CML, achieves complete hematologic response rates exceeding 90% and major cytogenetic response rates of 85-87% within 5 years, transforming CML from a fatal to a manageable with 10-year overall survival rates around 83%. In B-cell lymphomas, rituximab combined with regimens like CHOP (R-CHOP) has significantly enhanced outcomes in , increasing 5-year overall survival from 47% with CHOP alone to 58% with the addition of rituximab. This combination also improves event-free survival in and , with complete response rates rising by 20-30% compared to monotherapy. Basket trials have facilitated tumor-agnostic approvals for non-immunotherapeutic targeted agents, broadening access across cancer types based on shared molecular alterations. For instance, and are FDA-approved for NTRK fusion-positive solid tumors regardless of , achieving ORR of 75% and durable responses exceeding 12 months in pediatric and adult patients. for RET fusion-positive cancers and the BRAF inhibitor combination plus trametinib for BRAF V600E-mutant tumors similarly enable histology-independent treatment, with ORR around 40-64% in diverse solid tumors. Combination strategies integrating targeted therapies with or further optimize outcomes in . In EGFR-mutant NSCLC, combined with platinum-based as first-line therapy significantly prolongs PFS to 25.5 months compared to 16.7 months with monotherapy, reducing the risk of progression by 38%. As of 2025, KRAS G12C inhibitors have expanded targeted options for previously undruggable mutations across multiple cancers. , initially approved for KRAS G12C-mutant NSCLC, received expanded approval in combination with for pretreated KRAS G12C-mutant , demonstrating an ORR of 26% and median PFS of 5.6 months. demonstrates efficacy in phase III trials with ORR of 32% and median PFS of 5.5 months versus in pretreated KRAS G12C-mutant NSCLC. Emerging agents like divarasib have shown promising results in phase 2 trials with ORR of 53% and median PFS of 13.1 months, while ongoing studies explore applications in pancreatic and other KRAS-driven tumors.

In Non-Oncologic Diseases

Targeted therapy has extended beyond to address various non-malignant conditions by modulating specific molecular pathways involved in disease . In autoimmune disorders, these therapies often target cytokines or signaling cascades that drive , while in infectious diseases, they inhibit pathogen-specific enzymes. Applications in cardiovascular and neurological conditions focus on regulators or protein aggregates, respectively, demonstrating the versatility of precision approaches in non-oncologic settings. In autoimmune diseases, monoclonal antibodies like , an anti-tumor factor (TNF) agent, were approved by the U.S. (FDA) on December 31, 2002, for reducing signs and symptoms and inhibiting structural damage in adults with moderately to severely active . (JAK) inhibitors, such as , represent another class; it received FDA approval on May 30, 2018, as the first oral therapy for adults with moderately to severely active , an , after inadequate response to conventional treatments. These agents exemplify how biologic modalities can selectively suppress aberrant immune responses without broad . For infectious diseases, targeted antivirals have revolutionized management through inhibition of enzymes. , a inhibitor, was approved by the FDA in and is primarily used as a pharmacokinetic booster in combination regimens to enhance the efficacy of other antiretrovirals by inhibiting the , preventing viral maturation. This approach has significantly improved outcomes in treatment by allowing lower doses and reducing resistance development. In cardiovascular diseases, proprotein convertase subtilisin/kexin type 9 () inhibitors target lipid pathways to manage hypercholesterolemia. , a , was approved by the FDA on August 27, 2015, as an adjunct to diet and maximally tolerated statins for adults with heterozygous or clinical atherosclerotic , achieving substantial reductions of 50-60%. By modulating degradation, it addresses a key driver of elevated levels. Neurological applications include therapies against protein misfolding in neurodegenerative disorders. , an anti-amyloid , received FDA approval on July 2, 2024, for early based on reduction in and slowing of cognitive decline by approximately 35% in phase 3 trials, though associated with risks such as brain edema and hemorrhage. This approval represents a milestone in Alzheimer's treatment, highlighting progress in translating effects to clinical outcomes. While targeted therapies have fewer approvals in non-oncologic diseases compared to , expansions continue, particularly in rare genetic disorders. Antisense oligonucleotides (), such as , approved by the FDA in 2016 for (SMA), modify to increase functional SMN protein; by 2025, efforts to optimize dosing regimens and extend applications to other rare neurological conditions underscore growing therapeutic reach.

Efficacy and Challenges

Advantages and Benefits

Targeted therapies offer enhanced precision by selectively inhibiting molecular targets specific to cancer cells, leading to higher response rates in patients with relevant biomarkers. For instance, in non-small cell lung cancer (NSCLC) harboring EGFR mutations, first-line treatment with EGFR tyrosine kinase inhibitors (TKIs) such as achieves an objective response rate (ORR) of approximately 70% in biomarker-positive subgroups, compared to around 40% with standard platinum-based . This selectivity improves and overall efficacy in genetically defined populations, enabling more effective tumor control without broadly affecting healthy tissues. A key benefit is the reduced incidence of severe systemic toxicities associated with conventional chemotherapy. Unlike chemotherapy, which often causes widespread side effects such as alopecia, severe nausea, vomiting, and myelosuppression, targeted therapies typically spare these, resulting in lower rates of such adverse events. For example, EGFR inhibitors may induce manageable skin rashes but avoid the profound gastrointestinal distress and hair loss common in cytotoxic regimens, thereby minimizing treatment interruptions and hospitalization risks. Targeted therapies significantly enhance patient through convenient for many agents, such as TKIs, allowing outpatient rather than frequent intravenous infusions. This approach reduces the logistical burden on patients, enables home-based treatment, and supports better daily functioning and psychological . In indolent diseases like chronic myeloid leukemia (CML), chronic oral dosing facilitates long-term adherence without disrupting normal activities. From an economic and societal perspective, targeted therapies promote cost-effectiveness in biomarker-selected subsets by concentrating resources on responsive patients, optimizing healthcare outcomes and advancing frameworks. In CML, imatinib's use has demonstrated favorable cost per compared to broader therapies for solid tumors. This targeted allocation reduces overall treatment costs through improved response durability and decreased need for supportive care. Long-term advantages include the potential for durable remissions, transforming previously fatal diseases into manageable chronic conditions. in CML, for example, induces complete hematologic remission in over 95% of patients and major cytogenetic responses in about 86%, allowing many to achieve sustained molecular control and even treatment-free remission in select cases. Such outcomes extend survival while maintaining functionality, redefining disease trajectories in responsive malignancies.

Limitations and Resistance

Targeted therapies often encounter primary resistance, where tumors do not initially respond due to intrinsic factors such as preexisting or alternative signaling pathways, and acquired resistance, which develops over time through adaptive mechanisms. A prominent example is the EGFR T790M secondary , which confers resistance to first- and second-generation EGFR inhibitors (TKIs) like and by increasing the enzyme's affinity for ATP, thereby reducing drug binding; this arises in approximately 60% of cases of acquired resistance in EGFR-mutated non-small cell (NSCLC). Similarly, pathway bypass mechanisms, such as MET , activate parallel signaling routes to sustain tumor growth despite EGFR inhibition; MET amplification occurs in 16-18% of cases resistant to third-generation TKIs like in advanced EGFR-mutated NSCLC. Tumor heterogeneity further complicates targeted therapy efficacy, as not all cancer cells within a tumor express the intended target, leading to incomplete responses and subclonal of resistant populations. Intratumoral heterogeneity manifests spatially and temporally through genomic , epigenetic variations, and microenvironmental influences, allowing diverse subclones to survive selective pressure from therapy. For instance, in NSCLC treated with EGFR-TKIs, heterogeneous subclones harboring resistance mutations like EGFR C797S or bypass alterations can emerge, driving even after initial tumor shrinkage. This clonal diversity underscores why targeted agents may eradicate sensitive cells while sparing resistant ones, contributing to disease progression in up to 50% of responsive cases within 9-13 months. Side effects of targeted therapies are frequently target-specific, reflecting on-target inhibition of normal tissues, though rare severe toxicities can occur. Anti-vascular endothelial growth factor (VEGF) agents, such as , commonly induce in 30-80% of patients by disrupting vascular , often requiring antihypertensive management. inhibitors (TKIs) like frequently cause due to gastrointestinal epithelial disruption, affecting up to 50% of users and typically managed with dose adjustments or supportive care. Rare but serious adverse events include (ILD), reported in 1-5% of EGFR-TKI recipients, potentially fatal and linked to prior lung conditions or smoking history, necessitating prompt discontinuation and intervention. Accessibility to targeted therapies remains a significant barrier, driven by high costs and the need for specialized genomic testing. In 2023, 95% of new anticancer therapies, including many targeted agents, launched at prices exceeding $100,000 per year , contributing to global spending of $252 billion in 2024. These expenses, coupled with requirements for molecular profiling (costing 3,000−3,000-5,000 per test), exacerbate disparities in low-resource settings, where access to such treatments for eligible patients in low- and middle-income countries is often limited due to and formulary challenges. Applicability is limited, as only 20-30% of advanced solid tumors harbor actionable genomic targets suitable for FDA-approved targeted therapies, leaving the majority reliant on non-precision approaches. In clinical trials from 2023-2025, resistance remains high, with acquired resistance emerging in over 50% of initially responsive patients within 1-2 years, often due to heterogeneous undetectable at baseline.

Future Directions

Recent Advancements

In the period from 2020 to 2023, significant progress in targeted therapy was marked by the approval of G12C inhibitors for non-small cell (NSCLC). received accelerated FDA approval in May 2021 as the first targeted agent for adult patients with G12C-mutated locally advanced or metastatic NSCLC after at least one prior , demonstrating an objective response rate of 36% in the CodeBreaK 100 trial. followed with accelerated FDA approval in December 2022 for the same indication, based on the KRYSTAL-1 trial results showing an objective response rate of 43% and median of 6.5 months. These approvals addressed a long-standing challenge in targeting the previously "undruggable" , expanding options for approximately 13% of NSCLC cases harboring the G12C . Next-generation inhibitors (TKIs) also advanced, with gaining FDA approval in December 2020 for following tumor resection in patients with early-stage EGFR-mutated NSCLC, supported by the ADAURA trial showing a 80% reduction in disease recurrence risk. This built on its earlier first-line approval for metastatic EGFR-mutated NSCLC, establishing it as a cornerstone in EGFR-targeted regimens. Antibody-drug conjugate (ADC) therapies expanded their reach, notably with (Enhertu) receiving FDA approval in August 2022 for unresectable or metastatic HER2-low after prior . The DESTINY-Breast04 demonstrated a median of 9.9 months versus 5.1 months with , broadening HER2-targeted treatment to about 55% of metastatic patients previously ineligible for HER2-directed . In January 2025, Enhertu received further FDA approval for hormone receptor-positive, HER2-low or HER2-ultralow metastatic following prior endocrine , based on the DESTINY-Breast06 showing a 36% reduction in progression or death risk. Integration of multi-omics approaches, particularly liquid biopsies using (ctDNA), has enabled real-time monitoring of resistance in targeted therapies. In NSCLC, ctDNA analysis detects emerging resistance mutations, such as EGFR T790M, allowing dynamic adjustments to TKI regimens with sensitivity exceeding 80% for actionable alterations. Studies in 2023-2024 confirmed ctDNA's utility in predicting progression up to 5 months earlier than , facilitating personalized interventions in over 70% of resistant cases. Combination strategies pairing TKIs with chemotherapy gained traction, exemplified by the 2024 approval of combined with and as first-line treatment for EGFR-mutated metastatic NSCLC, based on the FLAURA2 trial showing improved of 25.5 months versus 16.7 months with alone. Updated September 2025 data from FLAURA2 further demonstrated a 23% reduction in overall survival risk with the combination. By 2025, (AI) has optimized design for targeted therapies, reducing recruitment timelines by up to 30% through predictive matching of patients to biomarker-driven studies. AI algorithms analyzed multi-omics data to refine inclusion criteria and predict response biomarkers, accelerating enrollment in precision trials. Concurrently, pan-KRAS inhibitors advanced to phase III, with RMC-6236 entering the RASolute 302 trial in 2024-2025, comparing it to in KRAS-mutated solid tumors and showing preliminary objective response rates of 35% across G12 variants. Daraxonrasib also received FDA designation in June 2025 for KRAS G12-mutated , poised for phase III evaluation based on phase II data indicating durable responses.

Emerging Innovations

Emerging innovations in targeted therapy are poised to address longstanding challenges by expanding the repertoire of druggable targets and enhancing therapeutic precision beyond 2025. A key frontier involves degrading "undruggable" proteins, such as the , which drives many cancers but lacks conventional binding pockets. PROteolysis-Targeting Chimeras (PROTACs) and molecular glues represent transformative modalities that recruit E3 ubiquitin ligases to induce target protein ation and proteasomal degradation, bypassing the need for direct inhibition. For instance, preclinical PROTACs targeting have demonstrated selective degradation in cancer cells, with phase I trials anticipated by late 2025 to evaluate safety and efficacy in MYC-overexpressing tumors. Similarly, molecular glues, which stabilize novel protein-protein interactions to facilitate degradation, have shown promise against transcription factors like in models, offering a compact alternative to larger PROTAC molecules. Delivery innovations are advancing to improve specificity and reduce systemic toxicity. Nanoparticle-based systems, such as lipid or polymer nanoparticles conjugated with targeting ligands, enable controlled release and tumor-specific accumulation via the , potentially increasing drug bioavailability by up to 10-fold in solid tumors. Recent developments include galloylated liposomes that overcome biological barriers like the blood-brain barrier for cancers, enhancing penetration while minimizing off-target effects. In parallel, chimeric antigen receptor (CAR) T-cell therapies are evolving with synthetic targets, incorporating logic-gated receptors that activate only upon dual recognition to avoid on-target/off-tumor toxicity; these "armored" CARs, enhanced by modules for secretion, have entered early-phase trials for solid tumors by 2025. Countermeasures against resistance are focusing on dynamic strategies to sustain . Adaptive dosing regimens, which adjust intensity based on real-time tumor dynamics to suppress resistant subpopulations while preserving sensitive ones, exploit fitness costs in resistant cells, extending in preclinical models of by 2-3 times compared to continuous dosing. Vertical inhibition, targeting multiple nodes within the same signaling pathway (e.g., simultaneous blockade of RAS, MEK, and ERK), prevents adaptive feedback loops that reactivate pathways, as evidenced in KRAS-mutant xenografts where such combinations delayed resistance onset by over 50%. These approaches integrate pharmacodynamic monitoring to personalize schedules. Artificial intelligence (AI) and are revolutionizing predictive modeling and in targeted therapy. algorithms analyzing multi-omics datasets can forecast resistance mutations with 85-90% accuracy, enabling preemptive combination therapies; for example, AI-driven simulations of tumor evolution have identified novel vertical inhibition targets in BRAF-mutant melanomas. In de novo , generative AI models like variational autoencoders create novel small molecules optimized for undruggable targets, reducing design cycles from years to months, as demonstrated in PROTAC libraries for protein kinases. xAI-inspired large language models for molecular simulations further accelerate this by predicting binding affinities with near-experimental precision. Broader applications of targeted therapy are expanding into early detection and prevention, with projections indicating over 50% of cancer cases could receive personalized regimens by 2030 through integrated genomic screening. Multi-cancer early detection platforms using targeted assays aim to identify precancerous lesions, potentially reducing incidence by 20-30% via preventive interventions like PROTAC-based chemoprevention. Market analyses forecast the personalized sector to exceed $600 billion globally by 2030, driven by AI-enhanced personalization that matches therapies to individual molecular profiles.

References

  1. https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies
  2. https://pubmed.ncbi.nlm.nih.gov/23092598/
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636149/
  4. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/targeted-therapy
  5. https://www.cancer.org/cancer/managing-cancer/treatment-types/targeted-therapy/how-does-targeted-therapy-work.html
  6. https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/approved-drug-list
  7. https://www.cancer.org/cancer/managing-cancer/treatment-types/targeted-therapy.html
  8. https://www.nature.com/articles/s12276-022-00864-3
  9. https://www.ncbi.nlm.nih.gov/books/NBK379335/
  10. https://www.intechopen.com/chapters/67515
  11. https://www.vipergen.com/from-target-to-therapy-a-comprehensive-overview-of-the-drug-discovery-workflow/
  12. https://www.ohsu.edu/knight-cancer-institute/targeted-therapy-cancer
  13. https://pubmed.ncbi.nlm.nih.gov/18469827/
  14. https://pmc.ncbi.nlm.nih.gov/articles/PMC9842142/
  15. https://www.cmaj.ca/content/196/16/E558
  16. https://globalrph.com/2025/03/targeted-therapy-vs-immunotherapy-in-oncology-advancements-and-comparisons-since-2022/
  17. https://www.cancer.gov/about-cancer/treatment/types
  18. https://pmc.ncbi.nlm.nih.gov/articles/PMC8558533/
  19. https://www.massgeneralbrigham.org/en/about/newsroom/articles/targeted-therapy-immunotherapy
  20. https://oncodaily.com/oncolibrary/immune-oncology/targeted-therapy-vs-immunotherapy
  21. https://www.compassoncology.com/blog/hormone-therapy-vs.-targeted-therapy-for-breast-cancer-treatment
  22. https://pmc.ncbi.nlm.nih.gov/articles/PMC4687565/
  23. https://rupress.org/jem/article/208/12/2351/41074/100-years-of-Rous-sarcoma-virus-100-years-of-Rous
  24. https://www.molbiolcell.org/doi/10.1091/mbc.E21-08-0407
  25. https://www.nobelprize.org/prizes/medicine/1984/press-release/
  26. https://pubmed.ncbi.nlm.nih.gov/21337095/
  27. https://pmc.ncbi.nlm.nih.gov/articles/PMC6360858/
  28. https://www.cancer.gov/research/progress/discovery/her2
  29. https://www.sciencedirect.com/science/article/pii/S1074552103001947
  30. https://pmc.ncbi.nlm.nih.gov/articles/PMC4655606/
  31. https://jhoonline.biomedcentral.com/articles/10.1186/s13045-018-0624-2
  32. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=79793
  33. https://www.nature.com/articles/s41392-024-01856-7
  34. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/103792s5250lbl.pdf
  35. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21335_Gleevec.cfm
  36. https://www.nejm.org/doi/full/10.1056/NEJMoa062867
  37. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429s000TOC.cfm
  38. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/125427Orig1s000TOC.cfm
  39. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sotorasib-kras-g12c-mutated-nsclc
  40. https://www.evitria.com/journal/bispecific-antibodies/fda-approved-bispecific-antibodies/
  41. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-repotrectinib-lorlatinib-and-entrectinib-ros1-positive-non-small-cell-lung
  42. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tarlatamab-dltd-extensive-stage-small-cell-lung-cancer
  43. https://www.targetedonc.com/view/novel-combinations-highlight-treatment-advances-in-melanoma
  44. https://bmccancer.biomedcentral.com/articles/10.1186/s12885-018-4984-3
  45. https://www.aacr.org/blog/2025/11/05/new-molecular-targets-technologies-and-cancer-treatments-take-center-stage-at-the-aacr-nci-eortc-conference/
  46. https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.755053/full
  47. https://www.nature.com/articles/s41392-021-00572-w
  48. https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-018-0804-2
  49. https://pubmed.ncbi.nlm.nih.gov/17883287/
  50. https://www.nature.com/articles/s41392-019-0069-2
  51. https://pmc.ncbi.nlm.nih.gov/articles/PMC9636149/
  52. https://pmc.ncbi.nlm.nih.gov/articles/PMC9406325/
  53. https://www.nature.com/articles/s41392-025-02266-z
  54. https://www.news-medical.net/whitepaper/20250218/Anti-CD20-mAbs-profiling.aspx
  55. https://pmc.ncbi.nlm.nih.gov/articles/PMC3145341/
  56. https://www.pnas.org/doi/10.1073/pnas.1802354115
  57. https://pmc.ncbi.nlm.nih.gov/articles/PMC4145758/
  58. https://pmc.ncbi.nlm.nih.gov/articles/PMC4480224/
  59. https://www.nature.com/articles/s41573-020-0087-3
  60. https://www.nature.com/articles/ng.2764
  61. https://www.cancer.gov/ccg/research/genome-sequencing/tcga/history
  62. https://www.nature.com/articles/s12276-025-01487-0
  63. https://aacrjournals.org/cancerdiscovery/article/12/2/432/678482/An-In-Vivo-CRISPR-Screening-Platform-for
  64. https://pmc.ncbi.nlm.nih.gov/articles/PMC10195102/
  65. https://portlandpress.com/biochemj/article/480/6/403/232794/Principles-of-phosphoproteomics-and-applications
  66. https://www.nature.com/articles/s12276-024-01272-5
  67. https://pmc.ncbi.nlm.nih.gov/articles/PMC10702130/
  68. https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-024-00565-1
  69. https://www.nature.com/articles/s41392-024-01823-2
  70. https://pubs.rsc.org/en/content/articlelanding/2023/sc/d2sc05709c
  71. https://journals.sagepub.com/doi/10.1089/aipo.2024.0010
  72. https://blog.google/technology/ai/google-deepmind-isomorphic-alphafold-3-ai-model/
  73. https://www.sciencedirect.com/science/article/pii/S1359644622000733
  74. https://www.nejm.org/doi/full/10.1056/NEJM200104053441401
  75. https://www.nejm.org/doi/full/10.1056/NEJMoa050753
  76. https://www.nejm.org/doi/full/10.1056/NEJMoa1412690
  77. https://www.nature.com/articles/nrd2130
  78. https://aacrjournals.org/clincancerres/article/21/5/995/247889/CDK-4-6-Inhibitor-Palbociclib-PD0332991-in-Rb
  79. https://www.nature.com/articles/s41392-023-01469-6
  80. https://pmc.ncbi.nlm.nih.gov/articles/PMC7551545/
  81. https://pmc.ncbi.nlm.nih.gov/articles/PMC8448950/
  82. https://www.ncbi.nlm.nih.gov/books/NBK532246/
  83. https://pmc.ncbi.nlm.nih.gov/articles/PMC3512181/
  84. https://pmc.ncbi.nlm.nih.gov/articles/PMC7964163/
  85. https://pmc.ncbi.nlm.nih.gov/articles/PMC4558758/
  86. https://pmc.ncbi.nlm.nih.gov/articles/PMC2958569/
  87. https://pmc.ncbi.nlm.nih.gov/articles/PMC5022998/
  88. https://www.nature.com/articles/s41392-022-00947-7
  89. https://pmc.ncbi.nlm.nih.gov/articles/PMC12480482/
  90. https://pubs.acs.org/doi/10.1021/jm500766w
  91. https://www.biochempeg.com/article/269.html
  92. https://pubs.rsc.org/en/content/articlelanding/2021/nj/d0nj04134c
  93. https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.202300720
  94. https://www.mdpi.com/2072-6694/15/17/4381
  95. https://pubmed.ncbi.nlm.nih.gov/40583768/
  96. https://www.nejm.org/doi/full/10.1056/NEJMoa2107322
  97. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%252823%252900638-1/fulltext
  98. https://www.nature.com/articles/s41573-021-00371-6
  99. https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-00885-3
  100. https://www.nature.com/articles/s41598-025-86130-8
  101. https://pmc.ncbi.nlm.nih.gov/articles/PMC11794548/
  102. https://pmc.ncbi.nlm.nih.gov/articles/PMC5673844/
  103. https://www.nature.com/articles/s41392-025-02301-z
  104. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00083-X/abstract
  105. https://www.nature.com/articles/s41467-025-62350-4
  106. https://ascopubs.org/doi/10.1200/EDBK_390094
  107. https://pmc.ncbi.nlm.nih.gov/articles/PMC9640784/
  108. https://pmc.ncbi.nlm.nih.gov/articles/PMC10896056/
  109. https://pmc.ncbi.nlm.nih.gov/articles/PMC10183098/
  110. https://pmc.ncbi.nlm.nih.gov/articles/PMC5217519/
  111. https://pmc.ncbi.nlm.nih.gov/articles/PMC3377508/
  112. https://pmc.ncbi.nlm.nih.gov/articles/PMC5901965/
  113. https://pubmed.ncbi.nlm.nih.gov/15955905/
  114. https://pmc.ncbi.nlm.nih.gov/articles/PMC4938327/
  115. https://pmc.ncbi.nlm.nih.gov/articles/PMC11899253/
  116. https://pmc.ncbi.nlm.nih.gov/articles/PMC10144220/
  117. https://www.nejm.org/doi/full/10.1056/NEJMoa2306434
  118. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sotorasib-panitumumab-kras-g12c-mutated-colorectal-cancer
  119. https://ascopubs.org/doi/10.1200/JCO.2024.42.17_suppl.LBA8509
  120. https://ascopubs.org/doi/10.1200/JCO-25-00040
  121. https://pmc.ncbi.nlm.nih.gov/articles/PMC8901705/
  122. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/BLA_125057_S000_HUMIRA_APPROV.PDF
  123. https://www.pfizer.com/news/press-release/press-release-detail/pfizer_announces_u_s_fda_approves_xeljanz_tofacitinib_for_the_treatment_of_moderately_to_severely_active_ulcerative_colitis-0
  124. https://www.ncbi.nlm.nih.gov/books/NBK544312/
  125. https://www.amgen.com/newsroom/press-releases/2015/08/fda-approves-amgens-new-cholesterollowering-medication-repatha-evolocumab
  126. https://www.fda.gov/news-events/press-announcements/fda-approves-treatment-adults-alzheimers-disease
  127. https://pmc.ncbi.nlm.nih.gov/articles/PMC6510522/
  128. https://www.managedhealthcareexecutive.com/view/higher-dose-regimen-of-nusinersen-approval-delayed-by-fda-complete-response-letter
  129. https://www.nejm.org/doi/full/10.1056/NEJMoa0801575
  130. https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21184
  131. https://academic.oup.com/jncimono/article/2019/53/lgz008/5551349
  132. https://ashpublications.org/blood/article/114/22/4547/64219/Cost-Effectiveness-of-Targeted-Cancer-Therapies
  133. https://pmc.ncbi.nlm.nih.gov/articles/PMC4269853/
  134. https://www.nejm.org/doi/full/10.1056/NEJMoa1609324
  135. https://www.nejm.org/doi/full/10.1056/NEJMoa1411817
  136. https://www.nature.com/articles/s41467-023-35961-y
  137. https://www.nature.com/articles/s41416-019-0573-8
  138. https://cancerci.biomedcentral.com/articles/10.1186/s12935-025-03734-w
  139. https://www.cancer.org/cancer/types/lung-cancer/treating-non-small-cell/targeted-therapies.html
  140. https://pmc.ncbi.nlm.nih.gov/articles/PMC11848938/
  141. https://www.iqvia.com/insights/the-iqvia-institute/reports-and-publications/reports/global-oncology-trends-2025
  142. https://www.annalsofoncology.org/article/S0923-7534%2824%2904980-9/fulltext
  143. https://pmc.ncbi.nlm.nih.gov/articles/PMC12229528/
  144. https://www.sciencedirect.com/science/article/pii/S1535610823004415
  145. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-adagrasib-kras-g12c-mutated-nsclc
  146. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-adjuvant-therapy-non-small-cell-lung-cancer-egfr-mutations
  147. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fam-trastuzumab-deruxtecan-nxki-her2-low-breast-cancer
  148. https://www.nejm.org/doi/full/10.1056/NEJMoa2203690
  149. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2025/enhertu-approved-in-the-us-for-breast-cancer-post-et.html
  150. https://www.nature.com/articles/s41392-024-02021-w
  151. https://ascopubs.org/doi/10.1200/EDBK-25-481114
  152. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-chemotherapy-egfr-mutated-non-small-cell-lung-cancer
  153. https://www.onclive.com/view/frontline-osimertinib-plus-chemo-significantly-improves-os-in-egfr-mutated-advanced-nsclc
  154. https://www.aha.org/aha-center-health-innovation-market-scan/2025-10-21-how-ai-transforming-clinical-trials
  155. https://www.nature.com/articles/s44387-025-00044-4
  156. https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-announces-fda-breakthrough-therapy
  157. https://aacrjournals.org/cancerres/article/85/8_Supplement_2/LB193/761864/Abstract-LB193-Developing-protein-degraders-to
  158. https://www.tandfonline.com/doi/full/10.1080/10409238.2025.2564068?src=
  159. https://www.nature.com/articles/s41698-025-00931-8
  160. https://pubmed.ncbi.nlm.nih.gov/39825965/
  161. https://www.nature.com/articles/s41467-025-63198-4
  162. https://www.sciencedirect.com/science/article/pii/S1465324925007200
  163. https://www.nature.com/articles/s41388-025-03582-y
  164. https://aacrjournals.org/cancerres/article/85/18/3503/764448/Adaptive-Therapy-Exploits-Fitness-Deficits-in
  165. https://pmc.ncbi.nlm.nih.gov/articles/PMC7124991/
  166. https://oncodaily.com/oncolibrary/artificial-intelligence-in-cancer-drug-discovery
  167. https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-025-02321-x
  168. https://www.nature.com/articles/s44386-025-00029-y
  169. https://www.grandviewresearch.com/industry-analysis/multi-cancer-early-detection-market-report
  170. https://blackwaterbusinessconsulting.com/report/u-s-personalized-cancer-therapies-market/
  171. https://www.towardshealthcare.com/insights/targeted-therapy-market-sizing
Add your contribution
Related Hubs
User Avatar
No comments yet.