Gut Microbiota and Therapy in Metastatic Melanoma: Focus on MAPK Pathway Inhibition.

Gut microbiome (GM) and its either pro-tumorigenic or anti-tumorigenic role is intriguing and constitutes an evolving landscape in translational oncology. It has been suggested that these microorganisms may be involved in carcinogenesis, cancer treatment response and resistance, as well as predispos...

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Bibliographic Details
Authors: Guardamagna, Mora, Berciano-Guerrero, Miguel-Angel, Villaescusa-González, Beatriz, Perez-Ruiz, Elisabeth, Oliver, Javier, Lavado-Valenzuela, Rocío, Rueda-Dominguez, Antonio, Barragán, Isabel, Queipo-Ortuño, María Isabel
Format: article
Publication Date:2022
Country:España
Institution:Instituto de Salud Carlos III (ISCIII)
Repository:Repisalud
Language:English
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/18837
Online Access:http://hdl.handle.net/20.500.12105/18837
Access Level:Open access
Keyword:gut microbiome
immune system
metastatic melanoma
Anti-Bacterial Agents
Fecal Microbiota Transplantation
Gastrointestinal Microbiome
Humans
Immune Checkpoint Inhibitors
Immunotherapy
Melanoma
Mitogen-Activated Protein Kinase Kinases
Neoplasms, Second Primary
Protein Kinase Inhibitors
Proto-Oncogene Proteins B-raf
Tumor Microenvironment
Description
Summary:Gut microbiome (GM) and its either pro-tumorigenic or anti-tumorigenic role is intriguing and constitutes an evolving landscape in translational oncology. It has been suggested that these microorganisms may be involved in carcinogenesis, cancer treatment response and resistance, as well as predisposition to adverse effects. In melanoma patients, one of the most immunogenic cancers, immune checkpoint inhibitors (ICI) and MAPK-targeted therapy-BRAF/MEK inhibitors-have revolutionized prognosis, and the study of the microbiome as a modulating factor is thus appealing. Although BRAF/MEK inhibitors constitute one of the main backbones of treatment in melanoma, little is known about their impact on GM and how this might correlate with immune re-induction. On the contrary, ICI and their relationship to GM has become an interesting field of research due to the already-known impact of immunotherapy in modulating the immune system. Immune reprogramming in the tumor microenvironment has been established as one of the main targets of microbiome, since it can induce immunosuppressive phenotypes, promote inflammatory responses or conduct anti-tumor responses. As a result, ongoing clinical trials are evaluating the role of fecal microbiota transplant (FMT), as well as the impact of using dietary supplements, antibiotics and probiotics in the prediction of response to therapy. In this review, we provide an overview of GM's link to cancer, its relationship with the immune system and how this may impact response to treatments in melanoma patients. We also discuss insights about novel therapeutic approaches including FMT, changes in diet and use of probiotics, prebiotics and symbiotics. Finally, we hypothesize on the possible pathways through which GM may impact anti-tumor efficacy in melanoma patients treated with targeted therapy, an appealing subject of which little is known.