Development of cancer is a complex multistage process that involves distinct biochemical and cellular alterations. The conventional treatment approaches are limited by the toxicity to normal tissues and development of resistance over a period of time. Ionizing radiation has been implicated both in the carcinogenesis as well as a therapeutic strategy for cancer control. New advances in radiation biology have helped in decreasing the dosage and also in localizing the effects to the tumor. However, majority of malignant tumors develop resistance to radiation over a period of time mainly due to anomalous functioning of diverse biological pathways including RTK signaling, NF-kB pathway, sphingomyelinase pathway, DNA damage signaling, redox signaling, apoptosis, chromatin remodelling and epigenetic regulation. Acquired radioresistance hence becomes a vital setback in successful cancer treatment creating a critical need to look for adjuvant therapies.
The efficacy of radiation is further improved by use of various agents which sensitize the cells to radiation, thereby boosting the mortality rate sustained by radiation. To develop clinically relevant radiosensitizers requires an approach combining radiation with standard cytotoxic chemotherapeutic agents. However, even this becomes a risky set-up owing to the fact that these chemotherapeutic agents have their own set of side effects which needs to be counteredChemointervention has emerged lately as a novel approach in both preventing the disease as well as to increase the efficiency of the treatment modules presently in use. Naturally occurring compounds like curcumin, parthenolide, genistein, gossypol, ellagic acid, withaferin, plumbagin, etc., which are generally safe for normal cells, are known to possess anticancer properties and have been studied to show synergistic effect along with radio- and chemotherapy, in addition to showing protection to normal tissues. We focus on current theories regarding the molecular mechanisms mediating radiation resistance and the chemomodulatory effects of phytochemicals in ionization radiation-mediated cancer therapy.