Metabolic reprogramming in cancer - signaling pathways and therapeutic targets

Sep 22, 2026

Metabolism underpins essential cellular life processes, and while metabolic dysregulation can impair normal cells and trigger senescence or apoptosis, tumor cells exploit metabolic remodeling as a driver of growth and proliferation. Cancer heterogeneity and plasticity create distinct energy-metabolism adaptations, tightly linked to metabolic crosstalk within the tumor microenvironment. Glycolysis, alongside amino acid, lipid, and polyamine metabolism, supports malignant progression and shapes microenvironmental cell fate. Targeting these pathways and interactions offers therapeutic promise, and this review consolidates metabolic redistribution from cell-autonomous reprogramming to microenvironment-mediated synergy.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages40

Reading Time1 h 41 min

AccessFree to download

Abstract

Introduction

Cancer incidence and treatment challenges

Metabolic reprogramming as a hallmark

Graphical Abstract

Modes of metabolic remodeling and therapeutic strategies

Dong and Li Molecular Cancer (2026) 25:60 [https://doi.org/10.1186/s12943-026-02582-0](https://doi.org/10.1186/s12943-026-02582-0) Molecular Cancer REVIEW Open Access Metabolic reprogramming in cancer: signaling pathways and therapeutic targets Shi Dong1,2 and Taiyuan Li 1,2* Abstract Metabolism is a general term for an ordered series of chemical reactions used to maintain life, and the maintenance of normal cellular activities cannot be separated from metabolism, which is the most basic feature of life. However, metabolic alterations have a dual role. In normal cells, metabolic dysregulation predisposes them to impaired energy acquisition, senescence and even apoptosis. In contrast, metabolic remodeling in tumor cells is advantageous for cancer cell growth and proliferation, driving tumor development and becoming a hallmark of cancer. The inherent heterogeneity and plasticity of many tumor cells themselves are often accompanied by unique alterations in energy metabolism that allow them to survive even in harsh environments where resources are scarce. Notably, tumor cells do not operate in isolation; their metabolic reprogramming is tightly intertwined with metabolic crosstalk and collaborative adaptations involving other components within the tumor microenvironment. Among these metabolic pathways, glycolysis remains the dominant metabolic pathway driving tumor growth and microenvironmental remodeling, even under oxygen-sufficient conditions. Additionally, amino acid, lipid, and polyamine metabolism have been identified as a metabolic regulators that support cancer cell growth, influencing the fate and function of other cells in the microenvironment through metabolite exchange. Targeting cancer metabolism and its interactions with the microenvironment has thus emerged asa promising strategy for treating various malignancies. This article systematically reviews the redistribution of metabolic activities during cancer progression, encompassing both cell-autonomous metabolic reprogramming and microenvironment-mediated metabolic synergy and adaptation. The aim is to provide novel insights and therapeutic strategies for the comprehensive treatment of cancer. Keywords Metabolic reprogramming, Glucose, Glutamine, Lipid, Polyamine, Tumor microenvironment, Cancer Introduction as smoking, aging, and other multifactorial risks, are Cancer has emerged as a major global health challenge in the 21st century, with the number of new cases projected to reach 35 million by 2050 [1, 2]. Notably, lung, breast, colorectal, prostate, and gastric cancers collectively account for more than half of all newly diagnosed cancer cases worldwide [2]. Persistent driving forces, such *Correspondence: Taiyuan Li[jylitaiyuan@sina.com](jylitaiyuan@sina.com) Full list of author information is available at the end of the article responsible for this increasing incidence [3]. However, this severe situation, although traditional cancer treatment methods have made significant progress driven by technology and research, numerous factors such as drug resistance and tumor heterogeneity, have prevented some cancer patients from benefiting. In particular, for patients with advanced cancer, the current treatment options encounter major challenges; thus, new treatment strategies are urgently needed. Metabolic reprogramming represents a critical hallmark of tumor cells. Unlike normal cells, cancer cells © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The

FAQs

What is the dual role of metabolic alterations in cancer?

In normal cells, metabolic dysregulation can lead to impaired energy acquisition, senescence, and apoptosis. In tumor cells, metabolic remodeling supports growth and proliferation, becoming a hallmark of cancer.

How does tumor metabolic reprogramming relate to the tumor microenvironment?

Tumor metabolic reprogramming is intertwined with metabolic crosstalk, involving coordinated adaptations across components of the tumor microenvironment through metabolite exchange.

Why is glycolysis emphasized as a key metabolic pathway in cancer?

Glycolysis remains the dominant metabolic pathway driving tumor growth and microenvironmental remodeling, including under oxygen-sufficient conditions.

Sep 22, 2026

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