Metabolic reprogramming in colorectal cancer - Mechanisms and therapeutic insights

Sep 22, 2026

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Metabolic reprogramming drives tumor medication resistance, recurrence, and malignant progression in colorectal cancer. This review methodically examines molecular changes in colorectal cancer metabolism, emphasizing how metabolic remodeling shapes and is shaped by the tumor microenvironment and major signaling pathways. It highlights metabolic characteristics that can enable discovery of new metabolic biomarkers, supporting earlier diagnosis and more personalized treatment strategies. The synthesis also discusses clinical translational value and links metabolic shifts to metastasis.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages28

Reading Time1 h 11 min

AccessFree to download

Introduction

The basic mechanisms of metabolic reprogramming

Glucose metabolic reprogramming

Aerobic glycolysis in CRC

Genes & Diseases (2027) 14, 102054 Available online [at](at www.sciencedirect.com)[ www.sciencedirect.com](at www.sciencedirect.com) ScienceDirect journal [homepage:](homepage: www . keaipublishing. com/en/journals/genes-diseases)[ www . keaipublishing. com/en/journals/genes-diseases](homepage: www . keaipublishing. com/en/journals/genes-diseases) REVIEW ARTICLE Metabolic reprogramming in colorectal cancer: Mechanisms and therapeutic insights Wen Xiao a, Dan Tan a, Wen Zeng b, Xiaoming Nie b, Mingliang Wang a,* a Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China b Department of Surgical Oncology, Ganzhou Cancer Hospital, Gannan Medical University, Ganzhou, Jiangxi 341000, China Received 14 February 2025; received in revised form 14 October 2025; accepted 11 December 2025 Available online 28 January 2026 KEYWORDS Colorectal cancer; Drug resistance; Metabolic reprogramming; Metastasis; Warburg effect Abstract Metabolic reprogramming is an important factor contributing to tumor medication resistance and recurrence in cancer cells. There is ample proof that metabolic remodeling is vital in colorectal cancer’s genesis, progression, and resistance to treatment. The molecular processes behind changes in metabolism in colorectal cancer are methodically examined in this review, including its interactions with the tumor microenvironment and key signaling pathways, and its potential clinical translational value. Investigating the metabolic characteristics of colorectal cancer and identifying novel metabolic biomarkers will provide essential support for early diagnosis and personalized therapy. ª 2026 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY license ([http://creativecommons.org/](http://creativecommons.org/)[ ](http://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/) ) . Introduction Colorectal cancer (CRC) accounts for 9.6% of the global cancer burden, rendering it the third most frequent cancer worldwide, following lung carcinoma and breast carcinoma. It is also the second most common cause of cancer deaths, * Corresponding author. E-mail [address:](address: wml_2902@163.com)[ wml_2902@163.com](address: wml_2902@163.com) (M. Wang). Peer review under the responsibility of Chongqing Medical University. responsible for approximately 9.3% of all cancer-related mortality rates.1 At the time of diagnosis, approximately one-fifth of CRC patients already have distant metastasis, while another quarter of them are initially diagnosed with confined cancer that might eventually progress to metastases.2 At this stage, surgical excision, chemotherapy, and radiation are the primary therapeutic choices for CRC. Unfortunately, the resistance, recurrence, and metastasis following radical resection are major causes of cancerrelated mortality.3 ,4 Since most CRC patients present with symptoms at an advanced stage, exploring novel biomarkers is of great significance for improving early [https://doi.org/10.1016/j.gendis.2026.102054](https://doi.org/10.1016/j.gendis.2026.102054) 2352-3042/ª 2026 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY license ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)). screening methods, optimizing personalized treatment, and reducing mortality.5 Metabolism encompasses a web of biological processes that transform nutrients into tiny molecules, commonly referred to as metabolites.6 ,7 By means of a series of metabolic transformations and the metabolites that are produced, cellular systems generate the energy, reducing equivalents, and macromolecules essential for cellular homeostasis and viability. Mutations of oncogenes and tumor suppressor genes induce metabolic reprogramming

FAQs

Why is metabolic reprogramming important in colorectal cancer?

Metabolic reprogramming contributes to tumor medication resistance, recurrence, and overall progression in colorectal cancer by reshaping how cancer cells use nutrients to support survival and growth.

What metabolic pathway is highlighted as a key feature of colorectal cancer?

The review emphasizes aerobic glycolysis, commonly known as the Warburg effect, where glucose is converted to lactate even under oxygen-rich conditions.

How does metabolic remodeling relate to the tumor microenvironment and signaling pathways?

The document explains that metabolic changes interact with the tumor microenvironment and key signaling pathways, influencing how colorectal cancer develops, advances, and resists treatment.

Sep 22, 2026

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