Signaling pathways in cancer metabolism: mechanisms and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 10, 2023

Abstract A wide spectrum of metabolites (mainly, the three major nutrients and their derivatives) can be sensed by specific sensors, then trigger a series signal transduction pathways affect expression levels genes in epigenetics, which is called metabolite sensing. Life body regulates metabolism, immunity, inflammation sensing, coordinating pathophysiology host to achieve balance with external environment. Metabolic reprogramming cancers cause different phenotypic characteristics cancer cell from normal cell, including proliferation, migration, invasion, angiogenesis, etc. disorders cells further create microenvironment many kinds oncometabolites that are conducive growth cancer, thus forming vicious circle. At same time, exogenous also biological behavior tumors. Here, we discuss sensing mechanisms derivatives, as well abnormalities development various cancers, potential therapeutic targets based on metabolite-sensing signaling prevent progression cancer.

Language: Английский

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Microbiota-Centered Interventions: The Next Breakthrough in Immuno-Oncology?

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(10), P. 2396 - 2412

Published: Aug. 16, 2021

The cancer-immune dialogue subject to immuno-oncological intervention is profoundly influenced by microenvironmental factors. Indeed, the mucosal microbiota-and more specifically, intestinal ecosystem-influences tone of anticancer immune responses and clinical benefit immunotherapy. Antibiotics blunt efficacy checkpoint inhibitors (ICI), fecal microbial transplantation may restore responsiveness ICI-resistant melanoma. Here, we review yin yang bacteria at crossroads between barrier, metabolism, local or systemic during therapies. We discuss diagnostic tools identify gut dysbiosis future prospects microbiota-based therapeutic interventions. SIGNIFICANCE: Given recent proof concept potential in patients with melanoma primarily resistant PD-1 blockade, it timely how why antibiotics compromise cancer immunotherapy, describe balance beneficial harmful species play therapies, introduce for microbiota-centered interventions immuno-oncology.

Language: Английский

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Oral administration of Akkermansia muciniphila elevates systemic antiaging and anticancer metabolites

Aging, Journal Year: 2021, Volume and Issue: 13(5), P. 6375 - 6405

Published: March 2, 2021

teaching and research institutions in France or abroad, from public private centers.L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques niveau recherche, publiés ou non, émanant des établissements d'enseignement recherche français étrangers, laboratoires publics privés.

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Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer

Cancer Discovery, Journal Year: 2021, Volume and Issue: 12(1), P. 90 - 107

Published: Nov. 17, 2021

Abstract In tumor-bearing mice, cyclic fasting or fasting-mimicking diets (FMD) enhance the activity of antineoplastic treatments by modulating systemic metabolism and boosting antitumor immunity. Here we conducted a clinical trial to investigate safety biological effects cyclic, five-day FMD in combination with standard therapies. 101 patients, was safe, feasible, resulted consistent decrease blood glucose growth factor concentration, thus recapitulating metabolic changes that mediate fasting/FMD anticancer preclinical experiments. Integrated transcriptomic deep-phenotyping analyses revealed profoundly reshapes immunity inducing contraction peripheral immunosuppressive myeloid regulatory T-cell compartments, paralleled enhanced intratumor Th1/cytotoxic responses an enrichment IFNγ other immune signatures associated better outcomes patients cancer. Our findings lay foundations for phase II/III trials aimed at investigating efficacy treatments. Significance: Cyclic is well tolerated causes remarkable different tumor types treated concomitant addition, immunity, finally activating several programs. Phase are needed activity/efficacy. This article highlighted Issue feature, p. 1

Language: Английский

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Dietary regulation in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 23, 2022

Nutriments have been deemed to impact all physiopathologic processes. Recent evidences in molecular medicine and clinical trials demonstrated that adequate nutrition treatments are the golden criterion for extending healthspan delaying ageing various species such as yeast, drosophila, rodent, primate human. It emerges develop precision-nutrition therapeutics slow age-related biological processes treat diverse diseases. However, nutritive advantages frequently diversify among individuals well organs tissues, which brings challenges this field. In review, we summarize different forms of dietary interventions extensively prescribed improvement disease treatment pre-clinical or clinical. We discuss nutrient-mediated mechanisms including metabolic regulators, metabolism pathways, epigenetic circadian clocks. Comparably, describe diet-responsive effectors by influence endocrinic, immunological, microbial neural states responsible improving health preventing multiple diseases humans. Furthermore, expatiate patterns dietotheroapies, fasting, calorie-restricted diet, ketogenic high-fibre plants-based protein restriction diet with specific reduction amino acids microelements, potentially affecting morbid states. Altogether, emphasize profound nutritional therapy, highlight crosstalk explored critical factors individualized therapeutic approaches predictors.

Language: Английский

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Emerging therapies in cancer metabolism

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(8), P. 1283 - 1303

Published: Aug. 1, 2023

Language: Английский

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Tumor acidity: From hallmark of cancer to target of treatment

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Aug. 29, 2022

Tumor acidity is one of the cancer hallmarks and associated with metabolic reprogramming use glycolysis, which results in a high intracellular lactic acid concentration. Cancer cells avoid stress major by activation expression proton lactate transporters exchangers have an inverted pH gradient (extracellular pHs are alkaline, respectively). The shift tumor acid-base balance promotes proliferation, apoptosis avoidance, invasiveness, metastatic potential, aggressiveness, immune evasion, treatment resistance. For example, weak-base chemotherapeutic agents may substantially reduced cellular uptake capacity due to "ion trapping". Lactic negatively affects functions activated effector T cells, stimulates regulatory them express programmed cell death receptor 1. On other hand, inversion could be weakness that will allow development new promising therapies, such as tumor-targeted pH-sensitive antibodies pH-responsible nanoparticle conjugates anticancer drugs. regulation levels pharmacological inhibition proteins (monocarboxylate transporters, H

Language: Английский

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Control of immunity via nutritional interventions

Immunity, Journal Year: 2022, Volume and Issue: 55(2), P. 210 - 223

Published: Feb. 1, 2022

Nutrition affects all physiological processes including those linked to the development and function of our immune system. Here, we discuss recent evidence emerging concepts supporting idea that newfound relationship with nutrition in industrialized countries has fundamentally altered way which system is wired. This will be examined through lens studies showing mild or transient reductions dietary intake can enhance protective immunity while also limiting aberrant inflammatory responses. We further how trade-offs priorities begin emerge context severe nutritional stress. In settings, specific immunological functions are heightened re-enforce tissue sites most critical survival. Altogether, these examples emphasize profound influence over highlight a mechanistic exploration this cross talk could ultimately lead design novel therapeutic approaches prevent treat disease.

Language: Английский

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Ketogenesis Attenuates KLF5-Dependent Production of CXCL12 to Overcome the Immunosuppressive Tumor Microenvironment in Colorectal Cancer

Cancer Research, Journal Year: 2022, Volume and Issue: 82(8), P. 1575 - 1588

Published: March 21, 2022

The dynamic composition of the tumor microenvironment (TME) can markedly alter response to targeted therapies for colorectal cancer. Cancer-associated fibroblasts (CAF) are major components TMEs that direct and induce infiltration immunosuppressive cells through secreted cytokines such as CXCL12. Ketogenic diets (KD) inhibit growth enhance anticancer effects immune checkpoint blockade. However, role ketogenesis on TME is not known. Here, we show decreased a signature cancer an increase in using KD decreases CXCL12 production tumors, serum, liver, lungs. Moreover, increasing by overexpression ketogenic enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) or treatment with ketone body β-hydroxybutyrate expression KLF5, which binds promoter induces CAFs. intratumoral accumulation cells, increased natural killer cytotoxic T enhanced PD-1 blockade murine-derived Furthermore, inhibited migration, invasion, metastasis vitro vivo. Overall, downregulated TME, represses KLF5-dependent improve leads efficacy immunotherapy reduced metastasis. Importantly, this work demonstrates downregulation de novo critical step progression.This study identifies regulator suggests potential metabolic strategy overcome immunosuppression prolong survival. See related commentary Montrose Galluzzi, p. 1464.

Language: Английский

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Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 11, 2024

Abstract Diet, serving as a vital source of nutrients, exerts profound influence on human health and disease progression. Recently, dietary interventions have emerged promising adjunctive treatment strategies not only for cancer but also neurodegenerative diseases, autoimmune cardiovascular metabolic disorders. These demonstrated substantial potential in modulating metabolism, trajectory, therapeutic responses. Metabolic reprogramming is hallmark malignant progression, deeper understanding this phenomenon tumors its effects immune regulation significant challenge that impedes eradication. Dietary intake, key environmental factor, can tumor metabolism. Emerging evidence indicates might affect the nutrient availability tumors, thereby increasing efficacy treatments. However, intricate interplay between pathogenesis other diseases complex. Despite encouraging results, mechanisms underlying diet-based remain largely unexplored, often resulting underutilization management. In review, we aim to illuminate various interventions, including calorie restriction, fasting-mimicking diet, ketogenic protein restriction high-salt high-fat high-fiber aforementioned diseases. We explore multifaceted impacts these encompassing their immunomodulatory effects, biological impacts, molecular mechanisms. This review offers valuable insights into application therapies

Language: Английский

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