Metabolic crossroads: unravelling immune cell dynamics in gastrointestinal cancer drug resistance

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Metabolic reprogramming within the tumor microenvironment (TME) plays a critical role in driving drug resistance gastrointestinal cancers (GI), particularly through pathways of fatty acid oxidation and glycolysis. Cancer cells often rewire their metabolism to sustain growth reshape TME, creating conditions such as nutrient depletion, hypoxia, acidity that impair antitumor immune responses. Immune TME also undergo metabolic alterations, frequently adopting immunosuppressive phenotypes promote progression reduce efficacy therapies. The competition for essential nutrients, glucose, between cancer compromises functions effector cells, T cells. Additionally, by-products like lactate kynurenine further suppress activity populations, including regulatory M2 macrophages. Targeting glycolysis presents new opportunities overcome improve therapeutic outcomes GI cancers. Modulating these key has potential reinvigorate exhausted shift toward phenotypes, enhance effectiveness immunotherapies other treatments. Future strategies will require continued research into metabolism, development novel inhibitors, clinical trials evaluating combination Identifying validating biomarkers be crucial patient stratification treatment monitoring. Insights may have broader implications across multiple types, offering avenues improving treatment.

Language: Английский

Unraveling the nexus: Genomic instability and metabolism in cancer

Cell Reports, Journal Year: 2025, Volume and Issue: 44(4), P. 115540 - 115540

Published: April 1, 2025

The DNA-damage response (DDR) is a signaling network that enables cells to detect and repair genomic damage. Over the past three decades, inhibiting DDR has proven be an effective cancer therapeutic strategy. Although drugs targeting have received approval for treating various cancers, tumor often develop resistance these therapies, owing their ability undergo energetic metabolic reprogramming. Metabolic intermediates also influence cells' sense oxidative stress, leading impaired redox metabolism, thus creating vulnerabilities. In this review, we summarize recent advances in understanding crosstalk between metabolism. We discuss combination therapies target DDR, vulnerabilities cancer. outline potential obstacles metabolism propose strategies overcome challenges.

Language: Английский

Cancer metabolic reprogramming and precision medicine-current perspective

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 17, 2024

Despite the advanced technologies and global attention on cancer treatment strategies, continues to claim lives adversely affects socio-economic development. Although combination therapies were anticipated eradicate this disease, resilient restorative nature of cancers allows them proliferate at expense host immune cells energetically. This proliferation is driven by metabolic profiles specific type patient. An emerging field exploring reprogramming (MR) predict effective treatments. mini-review discusses recent advancements in MR that have contributed predictive, preventive, precision medicine. Current perspectives mechanisms various types prospects for personalized medicine are essential optimizing outputs necessary

Language: Английский