A radiosensitizer is an agent that makes

tumor cells A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

more sensitive to

radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

. It is sometimes also known as a radiation sensitizer or radio-enhancer.

Mechanism of action

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:

DNA Damage Enhancement

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.

Cell Cycle Interference

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.

Hypoxia Modification

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.

Limitations

One of the major limitations of radiotherapy is that the cells of solid tumors become deficient in oxygen. Solid tumors can outgrow their blood supply, causing a low-oxygen state known as hypoxia. Oxygen is a potent radiosensitizer, increasing the effectiveness of a given dose of radiation by forming DNA-damaging free radicals. Tumor cells in a hypoxic environment may be as much as 2 to 3 times more resistant to radiation damage than those in a normal oxygen environment. Much research has been devoted to overcoming this problem including the use of high pressure oxygen tanks, blood substitutes that carry increased oxygen, hypoxic cell radiosensitizers such as

misonidazole Misonidazole is a radiosensitizer that was investigated in clinical trials. It was used in these trials for radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provi ...

and

metronidazole Metronidazole, sold under the brand name Flagyl and Metrogyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vagino ...

, and hypoxic cytotoxins, such as

tirapazamine Tirapazamine ( SR-4233, WIN 59075) is an experimental anticancer drug that is activated to a toxic radical only at very low levels of oxygen ( hypoxia). Such levels are common in human solid tumors, a phenomenon known as tumor hypoxia. Thus, ti ...

Drug development

As of September 2016, there are a number of radiosensitizers in clinical trials.

References

{{NCI-cancer-dict

External links

Radiosensitizer
entry in the public domain NCI Dictionary of Cancer Terms Tumor markers