Radiotherapy is employed in the treatment of over half of all cancer patients in an effort to kill cancer cells. Many patients suffer adverse effects during and/or after treatment. Additionally, tumors recur in approximately half the patients treated with curative intent. Enhancing specific tumor killing and minimizing normal tissue damage from radiotherapy would improve tumor control and patient quality of life. Therapies with these effects are termed Radiation Modulators and are comprised of two broad categories:
- Radiosensitizers are agents intended to enhance tumor cell killing during radiation treatment while having a minimal effect on normal tissue.
- Radioprotectors/radiomitigators are agents given before and/or after any form of radiation treatment or exposure to prevent or reduce damage to normal tissues.
An ideal modulator for cancer treatment would both enhance radiation killing effects in tumors and protect the normal tissues.
Radioprotectors and mitigators are also being developed as potential countermeasures against nuclear/radiological terrorism or accidents.
There is an urgent and unmet need for safe, effective radiation modulators. To date, only one drug has received FDA approval for use as a radioprotector (amifostine). Unfortunately, this compound has multiple limitations to widespread clinical adoption including its need for IV administration and significant dose-limiting side effects.