Metabolic Interventions in Tumor Immunity: Focus on Dual Pathway Inhibitors

Chen, Min; Lan, Huanrong; Yao, Shiya; Jin, Ketao; Chen, Yun

doi:10.3390/cancers15072043

Cited by 2 publications

(3 citation statements)

References 183 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PI3K/Akt/mTOR, JAK-STAT, AMPK, and Wnt/β-catenin pathways have been strongly implicated with cancer metabolism. The PI3K/Akt/mTOR pathway dual inhibitors have exhibited a promising therapeutic effect [ 41 – 44 ] in cancer. Yang et al reported a dual inhibitor of AMPK and WNT/β-catenin which displayed promising anti-cancer activity against colorectal cancer [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Dual inhibition of glycolysis and glutaminolysis for synergistic therapy of rheumatoid arthritis

Ahmed,

Mahony,

Torres

et al. 2023

Arthritis Res Ther

View full text Add to dashboard Cite

Background Synovial fibroblasts in rheumatoid arthritis (RAFLS) exhibit a pathological aberration of glycolysis and glutaminolysis. Henceforth, we aimed to investigate if dual inhibition of these pathways by phytobiological compound c28MS has the potential of synergistic therapy for arthritis by targeting both glucose and glutamine metabolism. Methods The presence of HK2 and GLS across various cell types and associated gene expression in human synovial cells and a murine model of arthritis was evaluated by scRNA-seq. The metabolic profiling of RAFLS cells was done using H1-nuclear magnetic resonance spectroscopy under glycolytic and glutaminolytic inhibitory conditions by incubating with 3-bromopyruvate, CB839, or dual inhibitor c28MS. FLS functional analysis was conducted under similar conditions. ELISA was employed for the quantification of IL-6, CCL2, and MMP3. K/BxN sera was administered to mice to induce arthritis for in vivo arthritis experiments. Results scRNA-seq analysis revealed that many fibroblasts expressed Hk2 along with Gls with several genes including Ptgs2, Hif1a, Timp1, Cxcl5, and Plod2 only associated with double-positive fibroblasts, suggesting that dual inhibition can be an attractive target for fibroblasts. Metabolomic and functional analysis revealed that c28MS decreased the aggressive behavior of RAFLS by targeting both upregulated glycolysis and glutaminolysis. c28MS administered in vivo significantly decreased the severity of arthritis in the K/BxN model. Conclusion Our findings imply that dual inhibition of glycolysis and glutaminolysis could be an effective approach for the treatment of RA. It also suggests that targeting more than one metabolic pathway can be a novel treatment approach in non-cancer diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Despite the reported efficacy of these inhibitors, further research is needed for validation. And like all therapies, this approach has its downfalls as well, such as a lack of predictive biomarkers for the assessment of the treatment’s effectiveness, toxicity, or variance in efficacy according to the type of cancer [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Dual inhibition of glycolysis and glutaminolysis for synergistic therapy of rheumatoid arthritis

Ahmed,

Mahony,

Torres

et al. 2023

Arthritis Res Ther

View full text Add to dashboard Cite

show abstract

“…This creates a competitive environment for nutrients between tumors and immune cells, thereby influencing immune responses. The development of dual signaling pathway inhibitors targeting PI3K/AKT/mTOR and other pathways is underway to enhance cancer therapy [188,189].…”

Section: Metabolic Reprogramming and Topo-active Drug Resistancementioning

confidence: 99%

Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review

Sharma,

Bahot,

Sekar

et al. 2024

Cancers

View full text Add to dashboard Cite

In recent years, the emergence of cancer drug resistance has been one of the crucial tumor hallmarks that are supported by the level of genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression of ABC transporters, and stemness are among the several key contributing molecular and cellular response mechanisms. Topo-active drugs, e.g., doxorubicin and topotecan, are clinically active and are utilized extensively against a wide variety of human tumors and often result in the development of resistance and failure to therapy. Thus, there is an urgent need for an incremental and comprehensive understanding of mechanisms of cancer drug resistance specifically in the context of topo-active drugs. This review delves into the intricate mechanistic aspects of these intracellular and extracellular topo-active drug resistance mechanisms and explores the use of potential combinatorial approaches by utilizing various topo-active drugs and inhibitors of pathways involved in drug resistance. We believe that this review will help guide basic scientists, pre-clinicians, clinicians, and policymakers toward holistic and interdisciplinary strategies that transcend resistance, renewing optimism in the ongoing battle against cancer.

show abstract

Metabolic Interventions in Tumor Immunity: Focus on Dual Pathway Inhibitors

Cited by 2 publications

References 183 publications

Dual inhibition of glycolysis and glutaminolysis for synergistic therapy of rheumatoid arthritis

Dual inhibition of glycolysis and glutaminolysis for synergistic therapy of rheumatoid arthritis

Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review

Contact Info

Product

Resources

About