Kidney cancer, also known as
renal cell carcinoma (RCC), is one of the top 10 diagnosed
cancers in the USA, and the incidence is rising. Despite major improvements in
drug therapy strategies, RCC remains a deadly
malignancy if not found and removed in its early stages. RCC is so highly
drug-resistant that no effective life-prolonging regimen of cytotoxic
chemotherapy has been demonstrated for RCC, despite several decades of effort. It is also highly radiation-resistant, thus circumventing
therapies to prevent local recurrence or to control metastatic disease. In the last few years, extensive research has been conducted to elucidate the functional significance of the
plant-derived compounds, and their derivatives, as
anticancer agents. This review is focussed on a chemo-dietary prevention strategy against RCC using a citrus-derived compound called
2'-hydroxyflavanone. RCC is frequently caused by VHL gene mutations, which contribute to 75% of all RCCs. These mutations are positively linked to cigarette smoking, and exposure to the tobacco
carcinogen,
N-nitrosodimethylamine and benzopyrene, can disrupt VHL. According to in vitro and preclinical mouse studies,
2'-hydroxyflavanone can both protect the VHL locus and prevent the progression of VHL-mutant
cancer. Human clinical trials examining the effect of supplementation of
2'-hydroxyflavanone, either alone or in combination with chemotherapeutic drugs, on RCC prevention have not been conducted, although there is considerable potential for
2'-hydroxyflavanone and its derivatives to be developed as RCC
chemoprevention agents. Therefore, the discovery of plant-derived
cancer therapies, such as
2'-hydroxyflavanone, offers a new strategy for combating this highly resistant
cancer.