Cancer is one of the major health problems and the second cause of death worldwide behind
heart disease. The traditional soy diet containing
isoflavones, consumed by the Asian population in China and Japan has been identified as a protective factor from
hormone-related
cancers. Over the years the research focus has shifted from emphasizing the preventive effect of
isoflavones from
cancer initiation and promotion to their efficacy against established
tumors along with chemo- and radiopotentiating effects. Studies performed in mouse models and results of clinical trials emphasize that
genistein or a mixture of
isoflavones, containing in traditional soy diet, could be utilized to both potentiate the response of
cancer cells to
radiotherapy and reduce radiation-induced toxicity in normal tissues. Currently ongoing clinical research explores a potential of another significant
isoflavone, idronoxil, also known as
phenoxodiol, as radiation enhancing agent. In the light of the recent clinical findings, this article reviews the accumulated evidence which support the clinically desirable interactions of soy
isoflavones with
radiation therapy resulting in improved
tumor treatment. This review discusses important aspects of the development of
isoflavones as
anticancer agents, and mechanisms potentially relevant to their activity in combination with
radiation therapy of
cancer. It gives a critical overview of studies characterizing
isoflavone targets such as topoisomerases, ENOX2/PMET,
tyrosine kinases and ER receptor signaling, and cellular effects on the cell cycle, DNA damage, cell death, and immune responses.