Radiosensitizer

A radiosensitizer is an agent that makes tumor cells more sensitive to radiation therapy. It is sometimes also known as a radiation sensitizer or radio-enhancer.

Conventional chemotherapeutics are currently being used in conjunction with radiation therapy to increase its effectiveness. Examples include the fluoropyrimidines, gemcitabine and platinum analogs; fluoropyrimidines increase sensitivity by dysregulating S-phase cell cycle checkpoints in tumor cells. Gemcitabine progresses through a similar mechanism, causing cells in the S-phase to disrepair DNA damage caused by the radiation. Platinum analogs such as cisplatin inhibit DNA repair by cross linking strands, and so aggravate the effects of DNA damage induced by radiation. Mechanisms of Action Radiosensitizers enhance the effects of radiation therapy through various mechanisms, broadly classified as:

These agents increase DNA damage caused by radiation or inhibit its repair.

Halogenated pyrimidines: Incorporate into DNA, making it more susceptible to radiation damage. Platinum analogs: Create DNA crosslinks, preventing repair. PARP inhibitors: Block DNA repair enzymes, increasing damage.

These agents disrupt the cell cycle, increasing radiosensitivity at specific phases.

Taxanes: Arrest cells in the radiosensitive G2/M phase. Antimetabolites: Interfere with DNA synthesis, leading to cell cycle arrest.

These agents address low oxygen levels (hypoxia) in tumors, which can hinder radiation effectiveness.

Nitroimidazoles: Mimic oxygen, enhancing free radical formation in hypoxic cells. Oxygen delivery agents: Improve oxygen supply to tumors.