New preclinical findings appear to bolster the case that a mixture of dietary plant estrogens derived from soybeans could prove to be a promising treatment adjuvant, reducing radiation toxicity and even possibly enhancing antitumor efficacy. Soy supplementation appears to be safe and headlines about soy compounds will increase cancer patients’ interest in the dietary supplements, but clinical trials are needed.
Despite important advances in external-beam radiotherapy targeting that allow higher tumor doses with less irradiation of healthy, nontarget tissues, radiation-associated toxicities continue to limit radiotherapeutic benefits for many cancer patients through dose limitation and treatment disruptions.1-3 This has sparked a search for radiosensitizing and radiation-protective or mitigating agents that can increase tumor susceptibilities or help protect patients’ other tissues from acute and chronic radiation-associated toxicities.2,3
Hillman and colleagues investigated soybean isoflavones as a potential treatment that can both radiosensitize tumors while mitigating radiation toxicity in healthy tissues.1,4,5 Soy isoflavones are plant estrogens, first recognized as potential cancer chemopreventive agents by epidemiologists studying dietary intake and cancer risks.1,6,7 These naturally-occurring drugs are protein tyrosine kinase inhibitors (TKIs), estrogen receptor activators, and antioxidants.2,8
Early studies identified genistein as a particularly interesting soy isoflavone candidate for enhancing radiotherapy in preclinical models by upregulating tumor cell apoptosis (cell-suicide) gene pathways.9 Importantly, when administered alone, pure genistein increased lymph node metastasis.9,10 But the role of an apparently safer and potentially more efficacious mixture of genistein, daidzein, and other soy phytoestrogens in reducing acute radiotherapy toxicities in lung tissue has been under investigation in recent years.1,4,5,9