Skip to content
Review Open access

Beyond Glucose and Lipids: The Pivotal Role of Amino Acid Reprogramming in Shaping the Tumor Microenvironment and Guiding the Development of Novel Therapeutics

Aug 2026 · International Journal of Medical Sciences · Vol 23, pp. 2974 - 2992 · 0 citations · 129 references
Medicine

TL;DR

It is confirmed that amino acid metabolism acts as a core driver of tumor proliferation, immune evasion and therapeutic resistance, and the potential of metabolic-targeted strategies in overcoming drug resistance and improving clinical efficacy is clarified.

Abstract

Metabolic reprogramming is a hallmark of tumor initiation and progression. Previous studies have focused mainly on glucose and lipid metabolism, with emphasis on the Warburg effect and de novo lipogenesis. Based on the shift in research paradigms, this review focuses on amino acid metabolism, which has long been overlooked, and systematically elaborates how tumors hijack amino acid pathways to construct an immunosuppressive and protumor microenvironment. We confirm that amino acid metabolism acts as a core driver of tumor proliferation, immune evasion and therapeutic resistance. This paper further discusses the intricate regulatory crosstalk between amino acid metabolism and convent ional antitumor therapies, clarifying the potential of metabolic-targeted strategies in overcoming drug resistance and improving clinical efficacy. Deviating from the traditional perception that amino acids merely serve as auxiliary substances for glucose and lipid metabolism, we summarize their vital roles in remodeling the immunosuppressive tumor microenvironment and provide theoretical support for the clinical integration of precise metabolic targeted therapy and existing antitumor regimens combined with cutting-edge technologies.

Read PDF

Similar papers

Review Open access Aug 2026

Metabolic reprogramming in pancreatic cancer: interplay of glucose, lipid, and amino acid metabolism in tumor progression

This article systematically reviews the molecular mechanisms underlying the dysregulation of three major nutrient metabolic pathways—glucose, lipid, and amino acid metabolism—and their interconnected regulatory networks and suggests a novel approach to improving the prognosis of pancreatic cancer.

Ze-Liang Zhang, Ying Tian, Bo Zhang et al. · 0 citations
Review Open access Aug 2026

Targeting the metabolic dependencies of tumor-associated macrophages for cancer immunotherapy

Tumor-associated macrophages (TAMs) play a pivotal role in tumor progression and immune evasion, with recent evidence indicating that metabolic reprogramming is crucial in determining their functional phenotype. Alterations in glucose, amino acid, and lipid metabolism are central to the regulation of TAMs plasticity,...

Wei-Feng Yuan, Yi-Ran Zhu, Yu-Xin Zhang et al. · 0 citations
Review Aug 2026

Targeting metabolic reprogramming in cancer: Past, present, and future.

Cancer cells undergo profound metabolic reprogramming to sustain uncontrolled proliferation within a nutrient-limited and often hypoxic tumor microenvironment (TME). Metabolic rewiring is an active driver of oncogenesis, immune evasion, epigenetic remodeling, and therapy resistance. Over the past century, our understan...

Niti Kumari, Surendra K. Shukla, Ravi Thakur · 0 citations
Review Sep 2026

Lipid Metabolic Reprogramming in Colorectal Cancer: A Central Hub Integrating Diet, Microenvironment, and Therapy Resistance.

Colorectal cancer (CRC), a significant malignancy of the digestive system, represents a considerable threat to global health. Currently, its clinical efficacy is often limited by tumor heterogeneity and therapeutic resistance. Lipid metabolic reprogramming has been identified as a core process in CRC, not only providin...

Xiao-Ya Zong, Wei-Bing Zu, Dong Tang · 0 citations
Review Sep 2026

Targeting Nicotinamide Metabolism to Reprogram the Tumor Microenvironment: Mechanisms and Novel Therapeutic Strategies.

This review examines how nicotinamide (NAM) metabolism may contribute to malignant remodeling of the TME at three interconnected levels: fueling the hypermetabolic state of cancer cells and contributing to TME acidification; modulating tumor angiogenesis; and establishing and sustaining an immunosuppressive, chronic in...

Wei-Dong Sun, Shuang-Zhou Bi, Xiao-Juan Zhu et al. · 0 citations
Review Open access Aug 2026

Metabolic reprogramming and immune evasion interaction in the tumor microenvironment promote tumor progression

Emerging evidence demonstrates that tumor metabolic reprogramming not only supports tumor-cell proliferation but also promotes the establishment of an immunosuppressive tumor microenvironment (TME) by altering nutrient competition and metabolite accumulation. Therefore, metabolic reprogramming and immune evasion should...

Hai-Lun Wang, Han-Yuan Zhao, Xue-Lu Pu et al. · 0 citations

We use cookies to run the site and, with your consent, for analytics and to show ads. See our Cookie Policy.