Vitamin C’s essential role in DNA and histone demethylation and a preclinical rationale for its therapeutic high-dose potential in renal cell carcinoma

Renal cell carcinoma (RCC) accounts for 2–3% of all malignancies in adults and 85% of all cases of adult kidney cancer (1). With an insidious disease course, nearly 25–30% of patients will present with metastatic RCC (2). Otherwise, 30% of patients undergoing nephrectomy progress to distant metastasis or local recurrence during follow-up (3). It is important to be able to predict the risk of early RCC recurrence (4,5). The last two decades have witnessed the development of a number of targeted therapies including tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors, but these advancements have largely ignored first-line and subsequent therapies for patients with metastatic RCC (6). It is clear that there is a need for new therapy strategies in advanced RCC.