Vitamin C in the Treatment of Colorectal Cancer: Between Hope and Despair

Despite recent progress in different treatment modalities, colorectal cancer remains a leading cause of cancer-related death, highlighting the need to further develop novel treatment strategies. In this context, over recent decades, several experimental studies have demonstrated that high doses of vitamin C provide anti-cancer benefits in various colorectal cancer models. Intravenous administrations of vitamin C are necessary to reach these high concentrations in tumors. Tumors harboring <i>KRAS</i> or <i>BRAF</i> mutations or driven by the HIF1α signaling pathway are particularly sensitive to high-dose vitamin C. In addition, high doses of vitamin C increase the efficacy of other treatments when used in combination, including chemotherapies, targeted therapies, and immunotherapies. Whilst results of experimental studies were promising, their translation into clinical protocols has been disappointing. So far, very few clinical data support the anti-cancer benefits of vitamin C in colorectal cancer patients. This lack of success highlights the need to ameliorate the selection of patients based on biomarkers and to refine treatment protocols to achieve high-dose vitamin C in tumors. In this review, we analyze in vitro and in vivo studies that investigated the effect of vitamin C in colorectal cancer cells and point out the anti-cancer mechanisms of vitamin C. We further examine clinical trials that tested vitamin C in colorectal cancer patients and address several points that still need to be investigated in order to fully define the role of vitamin C in the treatment of colorectal cancer.