Cellular Signaling and Metabolic Adaptations in the Tumor Microenvironment
A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Metabolism".
Deadline for manuscript submissions: 20 July 2026 | Viewed by 8
Special Issue Editor
Special Issue Information
Dear Colleagues,
To sustain unchecked proliferation, cancer cells undergo profound metabolic adaptation to withstand the hostile tumor microenvironment (TME), characterized by nutrient scarcity, hypoxia, and metabolic stress. These adaptations arise from extensive transcriptional and signaling reprogramming that rewires cellular metabolism toward aerobic glycolysis, decouples glucose utilization from mitochondrial oxidation, and activates anaplerotic pathways. This metabolic rewiring supports biosynthetic demands while driving the accumulation and secretion of metabolites that function as signaling mediators, fostering intercellular crosstalk that promotes tumor progression and suppresses anti-tumor immunity.
Several oncogenic signaling axes serve as master regulators of metabolic plasticity, enabling cancer cells to integrate growth factors and nutrient signals and prioritize macromolecular synthesis required for rapid biomass expansion. Concurrently, stress-adaptive pathways activated by hypoxia and nutrient deprivation recalibrate metabolic fluxes to enhance efficiency and flexibility by favoring anaerobic metabolism and alternative nutrient sources.
Metabolic adaptation is further sculpted by dynamic interactions between cancer cells and stromal, immune, and vascular components of the TME, which collectively regulate nutrient availability, metabolite exchange, and waste accumulation. This intricate, dynamic network confers remarkable plasticity, propelling tumor progression, immune evasion, and therapeutic resistance, while simultaneously revealing metabolic vulnerabilities amenable to targeted intervention. Despite significant advances, the molecular complexity underlying cancer metabolic adaptation, particularly the interplay between intra- and intercellular signaling within the TME, remains poorly understood. Addressing this knowledge gap is critical for the development of novel therapeutic strategies.
This Special Issue aims to advance current knowledge of the signaling networks governing metabolic adaptation in cancer. We invite original research articles and reviews that explore metabolic plasticity driven by complex signaling interactions among cellular constituents of the tumor microenvironment.
Dr. Shashi Anand
Guest Editor
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Keywords
- cancer metabolic plasticity
- tumor microenvironment
- metabolic vulnerabilities
- oncogenic signaling pathways
- hypoxia and nutrient stress
- therapeutic resistance
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