Abstract

Simple SummaryColorectal cancer is a leading cause of death worldwide. Despite the development of novel surgical and therapeutic strategies, 50% of patients relapse after treatment. Therapy failure, due to low efficacy, adverse effects and drug resistance, is thus a major concern. The idea of combining standard therapy with non-toxic bioactive natural compounds is a recent topic in cancer research and aims to increase the efficacy of current antitumor therapies while reducing drug toxicity and adverse effects. In recent years, several studies have explored the capacity of polyphenols, dietary bioactive compounds enriched in fruit and vegetables, to act as adjuvants to improve colorectal cancer therapy. In the present review, we discuss these studies, highlighting the mechanisms underlying the adjuvant effect, and bring out the potential of this novel therapeutic approach as well as the critical issues related to clinical application.Colorectal cancer (CRC) is a major cancer type and a leading cause of death worldwide. Despite advances in therapeutic management, the current medical treatments are not sufficient to control metastatic disease. Treatment-related adverse effects and drug resistance strongly contribute to therapy failure and tumor recurrence. Combination therapy, involving cytotoxic treatments and non-toxic natural compounds, is arousing great interest as a promising more effective and safer alternative. Polyphenols, a heterogeneous group of bioactive dietary compounds mainly found in fruit and vegetables, have received great attention for their capacity to modulate various molecular pathways active in cancer cells and to affect host anticancer response. This review provides a summary of the most recent (i.e., since 2016) preclinical and clinical studies using polyphenols as adjuvants for CRC therapies. These studies highlight the beneficial effects of dietary polyphenols in combination with cytotoxic drugs or irradiation on both therapy outcome and drug resistance. Despite substantial preclinical evidence, data from a few pilot clinical trials are available to date with promising but still inconclusive results. Larger randomized controlled studies and polyphenol formulations with improved bioavailability are needed to translate the research progress into clinical applications and definitively prove the added value of these molecules in CRC management.

Highlights

  • Colorectal cancer (CRC) is the third most common and the second deadliest cancer in both males and females, with more than 900,000 deaths annually worldwide [1]

  • We provide a brief overview of the role of dietary polyphenols in CRC pathogenesis and treatment and summarize recent preclinical and clinical studies that have explored the capacity of these compounds to act as adjuvants to CRC therapies

  • A growing body of evidence indicates that CRC is a multi-factorial disease, with a variety of factors playing a role in its pathogenesis

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Summary

Introduction

Colorectal cancer (CRC) is the third most common and the second deadliest cancer in both males and females, with more than 900,000 deaths annually worldwide [1]. Over the past two decades, the survival rates of patients diagnosed with early stage CRC have significantly improved. There is an urgent need to explore novel non-toxic compounds that can be used in combination with standard treatments with the aim of reducing side effects, preventing resistance and improving tumor response to the current therapeutic options. Some natural compounds displayed additive or synergistic activities when combined with conventional cytotoxic therapies in CRC, opening the way to clinical translation [6]. We provide a brief overview of the role of dietary polyphenols in CRC pathogenesis and treatment and summarize recent preclinical and clinical studies that have explored the capacity of these compounds to act as adjuvants to CRC therapies. We discuss the relevance of these studies in filling some gaps in CRC management and some bottlenecks that may hamper the clinical translation of results

Pathogenesis and Clinical Management of Colorectal Cancer
Classification of Polyphenols and Dietary Sources
Biological Properties of Dietary Polyphenols
Role of Polyphenols in Colorectal Cancer Prevention and Treatment
Beneficial Effects of Polyphenols on Colorectal Cancer Treatment
Curcumin
Resveratrol
Other Dietary Polyphenols
Data from Clinical Trials
Findings
Conclusions
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