Decoding Cancer Metabolism: Recent Insights and Future Directions

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 15 April 2026 | Viewed by 1290

Special Issue Editors


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Guest Editor
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
Interests: cancer metabolism; immune metabolism; stem cells

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Guest Editor
Department of Cell, Developmental, & Integrative Biology, University of Alabama, Birmingham, AL 35233, USA
Interests: cancer biology; nanotechnology; cell biology; theranostics; immunotherapy

Special Issue Information

Dear Colleagues,

A major hallmark of cancer is the dysregulation of cellular energetics. Recent advances in the field of cancer metabolism have revealed critical insights into how cancer cells change their metabolic pathways to support rapid growth and survival. Researchers have identified the key alterations in metabolic processes, such as increased glycolysis (Warburg effect), enhanced fatty acid synthesis, and reliance on glutamine. Interestingly, different types of cancer cells rely on different metabolic pathways and rewire their metabolism accordingly to thrive in stress conditions. Technologies like metabolomics and advanced imaging techniques have allowed scientists to visualize these changes in real time and understand their implications for tumor behavior. Furthermore, the interplay between metabolism and the tumor microenvironment has become a significant focus, highlighting how cancer cells manipulate the surrounding cells and nutrients to their advantage. Targeting these metabolic pathways offers promising therapeutic strategies, with several novel drugs in clinical trials aimed at disrupting the metabolic adaptations of cancer cells. These advances are paving the way for more effective and personalized cancer treatments.

The purpose of this Issue is to highlight the recent findings in cancer metabolism. The goal of this Issue is to provide a broad scope that includes research papers and reviews related to the specific interactions between cancer cells and immune cells or other microenvironment cells. Furthermore, how cancer initiation, progression, and metastasis are linked with physiological metabolism alteration will be discussed, along with targeting cancer cell metabolism as a vulnerability to induce cell death and novel mechanisms on how different proteins/molecules regulate cancer metabolism.

Dr. Parash Prasad
Dr. Snehasis R. Mishra
Guest Editors

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Keywords

  • glutamine metabolism
  • Warburg effect
  • anaplerosis
  • fatty acid metabolism
  • ferroptosis
  • oncometabolites
  • hypoxia
  • mitochondrial dynamics
  • reactive oxygen species
  • glutathione synthesis
  • nutrient sensing

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Published Papers (1 paper)

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18 pages, 3064 KB  
Article
Inhibition of Tumor Microenvironment-Driven JAK-STAT Signaling Enhances Response to Arginine Deprivation Therapy in Triple-Negative Breast Cancer
by Hila Tishler, Shahar Ziman, Kuoyuan Cheng, Kun Wang, Neel Sanghvi, Lital Adler, Gil Stelzer, Hillary Maniriho, Bareket Dassa, Elizabeta Bab-Dinitz, Michal Levi, Sivan Galai, Omer Goldman, Yarden Ariav, Naama Darzi, Saar Ezagouri, Nitsan Nimni, Nataly Rosenfeld, Ron Rotkopf, Alexander Brandis, Tevie Mehlman, Roni Oren, Mirie Zerbib, Yuri Kuznetsov, Sara Donzelli, Giovanni Blandino, Rony Seger, Eytan Ruppin and Ayelet Erezadd Show full author list remove Hide full author list
Cells 2026, 15(1), 25; https://doi.org/10.3390/cells15010025 - 23 Dec 2025
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Abstract
Argininosuccinate synthetase 1 (ASS1) expression and arginine availability are key metabolic determinants that influence tumor fitness and regulate immune interactions within the tumor microenvironment (TME). Using an orthotopic triple-negative breast cancer (TNBC) model, we demonstrate that arginine deprivation heightens tumor dependence on the [...] Read more.
Argininosuccinate synthetase 1 (ASS1) expression and arginine availability are key metabolic determinants that influence tumor fitness and regulate immune interactions within the tumor microenvironment (TME). Using an orthotopic triple-negative breast cancer (TNBC) model, we demonstrate that arginine deprivation heightens tumor dependence on the TME for survival. Mechanistically, fibroblasts sustain tumor viability by supplying arginine, whereas macrophages cooperate with stromal cues to activate Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling, thereby enhancing tumor survival. Concordantly, a JAK-STAT gene-expression signature correlates with ASS1 levels in human TNBC datasets. Translationally, combined pharmacological inhibition of JAK signaling with arginine deprivation markedly suppresses tumor growth. Together, these findings reveal a TME-driven, targetable stromal–immune circuit that enables tumors to withstand arginine deficiency-induced metabolic stress. Broadly, our work highlights that mapping and strategically inducing metabolic dependencies can reveal actionable compensatory pathways, offering opportunities to improve cancer therapy. Full article
(This article belongs to the Special Issue Decoding Cancer Metabolism: Recent Insights and Future Directions)
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