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World J Gastrointest Oncol. Jun 15, 2022; 14(6): 1115-1123
Published online Jun 15, 2022. doi: 10.4251/wjgo.v14.i6.1115
Can dietary flavonoids be useful in the personalized treatment of colorectal cancer?
Cristina Pereira-Wilson
Cristina Pereira-Wilson, Department of Biology, Centre of Biological Engineering, LABBELS Associate Laboratory, University of Minho, Braga 4710-057, Portugal
Author contributions: Pereira-Wilson C is solely responsible for all aspects of this paper.
Supported by Portuguese Foundation for Science and Technology (FCT), No. UIDB/04469/2020; I&D&I AgriFood XXI, No. NORTE-01-0145-FEDER-000041; and Fundo Europeu de Desenvolvimento Regional (FEDER) through the NORTE 2020 program (Programa Operacional Regional do Norte 2014/2020).
Conflict-of-interest statement: The author has no conflict of interests.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Cristina Pereira-Wilson, PhD, Assistant Professor, Department of Biology, Centre of Biological Engineering, LABBELS Associate Laboratory, University of Minho, Campus de Gualtar, Braga 4710-057, Portugal. cpereira@bio.uminho.pt
Received: February 23, 2021
Peer-review started: February 23, 2021
First decision: May 3, 2021
Revised: May 23, 2021
Accepted: May 7, 2022
Article in press: May 7, 2022
Published online: June 15, 2022
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: Colorectal cancer, Personalized treatment, Quercetin, Curcumin, KRAS, BRAF

Core Tip: Given the limited efficacy of therapeutic strategies for colorectal cancer presenting mutational activations in mitogen-activated protein kinase and/or PI3K pathways, developing combination therapies with natural flavonoids with demonstrated effects on these pathways may constitute a valuable path forward. Published results show quercetin and curcumin as possibly the best candidates to be further explored in the context of adjuvant colorectal cancer therapy either as part of dietary prescriptions or as purified compounds in combination 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.