The pathogenesis and therapeutic implications of metabolic reprogramming in renal cell carcinoma DOI Creative Commons
Yifan Zhang, Shengli Zhang, Hongbin Sun

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 19, 2025

Abstract Renal cell carcinoma (RCC), a therapeutically recalcitrant genitourinary malignancy, exemplifies the profound interplay between oncogenic signaling and metabolic adaptation. Emerging evidence positions reprogramming as central axis of RCC pathogenesis, characterized by dynamic shifts in nutrient utilization that transcend canonical Warburg physiology to encompass lipid anabolism, glutamine auxotrophy, microenvironment-driven plasticity. This orchestrated rewiring cellular energetics sustains tumor proliferation under hypoxia while fostering immunosuppression through metabolite-mediated T exhaustion myeloid-derived suppressor activation. Crucially, exhibits heterogeneity across histological subtypes intratumoral regions—a feature increasingly recognized determinant therapeutic resistance. Our review systematically deciphers molecular architecture metabolism, elucidating how VHL/HIF mutations, mTOR pathway dysregulation, epigenetic modifiers converge reshape glucose flux, droplet biogenesis, amino acid catabolism. We present novel insights into spatial zonation within tumors, where pseudohypoxic niches engage lactate shuttling cholesterol efflux adjacent vasculature, creating pro-angiogenic immunosuppressive microdomains. Therapeutically, we evaluate first-in-class inhibitors targeting rate-limiting enzymes de novo lipogenesis proposing biomarker-driven strategies overcome compensatory highlight synergy glutaminase PD-1 blockade reinvigorating CD8 + function, role lipid-loaded cancer-associated fibroblasts shielding tumors from ferroptosis. Finally, outline translational roadmap integrating multi-omics profiling, functional metabolomics, biology match vulnerabilities with precision therapies.

Language: Английский

The role of B2M in cancer immunotherapy resistance: function, resistance mechanism, and reversal strategies DOI Creative Commons
Xiaowen Han,

Jiayi Zhang,

Weidong Li

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 21, 2025

Immunotherapy has emerged as a preeminent force in the domain of cancer therapeutics and achieved remarkable breakthroughs. Nevertheless, high resistance become most substantial impediment restricting its clinical efficacy. Beta-2 microglobulin (B2M), light chain major histocompatibility complex (MHC) class I, plays an indispensable part by presenting tumor antigens to cytotoxic T lymphocytes (CTLs) for exerting anti-tumor effects. Accumulating evidence indicates that B2M mutation/defect is one key mechanisms underlying immunotherapy resistance. Therefore, elucidating role played devising effective strategies battle against are pressing issues. This review will systematically expound upon them, aiming provide insight into potential promising target anticancer immune response.

Language: Английский

Citations

1
Citrate oscillations during cell cycle are a targetable vulnerability in cancer cells DOI Creative Commons
Philippe Icard, Marco Alifano, Luca Simula

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189313 - 189313

Published: April 1, 2025

Cell cycle progression is timely interconnected with oscillations in cellular metabolism. Here, we first describe how these metabolic allow cycling cells to meet the bioenergetic needs specifically for each phase of cell cycle. In parallel, highlight cytosolic level citrate dynamically regulated during different phases, being low G1 phase, increasing S peaking G2/M, and decreasing mitosis. Of note, cancer cells, a dysregulation such oscillation can support by promoting deregulated Warburg effect (aerobic glycolysis), activating oncogenic signaling pathways (such as PI3K/AKT), acetyl-CoA production via alternative routes, overconsumption acetate. Then, review administration sodium (at high doses) arrests G0/G1 or inhibits glycolysis PI3K/AKT, induces apoptosis, significantly reduces tumor growth various vivo models. Last, reason on possibility implement reinforce effectiveness inhibitors better cure cancer.

Language: Английский

Citations

0
The pathogenesis and therapeutic implications of metabolic reprogramming in renal cell carcinoma DOI Creative Commons
Yifan Zhang, Shengli Zhang, Hongbin Sun

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 19, 2025

Abstract Renal cell carcinoma (RCC), a therapeutically recalcitrant genitourinary malignancy, exemplifies the profound interplay between oncogenic signaling and metabolic adaptation. Emerging evidence positions reprogramming as central axis of RCC pathogenesis, characterized by dynamic shifts in nutrient utilization that transcend canonical Warburg physiology to encompass lipid anabolism, glutamine auxotrophy, microenvironment-driven plasticity. This orchestrated rewiring cellular energetics sustains tumor proliferation under hypoxia while fostering immunosuppression through metabolite-mediated T exhaustion myeloid-derived suppressor activation. Crucially, exhibits heterogeneity across histological subtypes intratumoral regions—a feature increasingly recognized determinant therapeutic resistance. Our review systematically deciphers molecular architecture metabolism, elucidating how VHL/HIF mutations, mTOR pathway dysregulation, epigenetic modifiers converge reshape glucose flux, droplet biogenesis, amino acid catabolism. We present novel insights into spatial zonation within tumors, where pseudohypoxic niches engage lactate shuttling cholesterol efflux adjacent vasculature, creating pro-angiogenic immunosuppressive microdomains. Therapeutically, we evaluate first-in-class inhibitors targeting rate-limiting enzymes de novo lipogenesis proposing biomarker-driven strategies overcome compensatory highlight synergy glutaminase PD-1 blockade reinvigorating CD8 + function, role lipid-loaded cancer-associated fibroblasts shielding tumors from ferroptosis. Finally, outline translational roadmap integrating multi-omics profiling, functional metabolomics, biology match vulnerabilities with precision therapies.

Language: Английский

Citations

0