Can dietary flavonoids be useful in the personalized treatment of colorectal cancer?

Abstract

Activating mutations in the oncogenes KRAS, BRAF and PI3K define molecular colorectal cancer (CRC) subtypes because they play key roles in promoting CRC development and in determining the efficacy of chemotherapeutic agents such as 5-fluorouracil and anti-epidermal growth factor receptor monoclonal antibodies. Survival of patients with cancers displaying these molecular profiles is low. Given the limited efficacy of therapeutic strategies for CRC presenting mutational activations in mitogen-activated protein kinase and/or PI3K pathways, developing combination therapies with natural flavonoids or other phytochemicals with demonstrated effects on these pathways (and little or no toxic effects) may constitute a valuable path forward. Much has been published on the anticancer effects of dietary phytochemicals. However, even an exhaustive characterization of potential beneficial effects produced by in vitro studies cannot be extrapolated to effects in humans. So far, the available data constitute a good starting point. Published results show quercetin and curcumin as possibly the best candidates to be further explored in the context of adjuvant CRC therapy either as part of dietary prescriptions or as purified compounds in combination regimens with the drugs currently used in CRC treatment. Clinical trial data is still largely missing and is urgently needed to verify relevant effects and for the development of more personalized treatment approaches.

Keywords: BRAF; Colorectal cancer; Curcumin; KRAS; Personalized treatment; Quercetin.

Figure 1

Signaling pathways and molecular targets of anti-colorectal cancer chemotherapeutic drugs and of dietary phytochemical constituents. Generated with BioRender.com. EGFR: Epidermal growth factor receptor; EGCG: Epigallocatechin-3-gallate; VEGFR: Vascular endothelial growth factor receptor.