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Abstract
Understanding the mechanisms of resistance to therapy in human cancer cells has become a multifaceted limiting factor to achieving optimal cures in cancer patients. Besides genetic and epigenetic alterations, enhanced DNA damage repair activity, deregulation of cell death, overexpression of transmembrane transporters, and complex interactions within the tumor microenvironment, other mechanisms of cancer treatment resistance have been recently proposed. In this review, we will summarize the preclinical and clinical studies highlighting the critical role of the microbiome in the efficacy of cancer treatment, concerning mainly chemotherapy and immunotherapy with immune checkpoint inhibitors. In addition to involvement in drug metabolism and immune surveillance, the production of microbiota-derived metabolites might represent the link between gut/intratumoral bacteria and response to anticancer therapies. Importantly, an emerging trend of using microbiota modulation by probiotics and fecal microbiota transplantation (FMT) to overcome cancer treatment resistance will be also discussed.
Highlights
Recent advances in cancer treatment and clinical implementation of precision medicine have brought about the improvements in both the disease-free survival and quality of life in cancer patients
The gut barrier of murine models was disrupted after cyclophosphamide treatment, leading to a higher permeability for commensal bacteria such as Lactobacillus johnsonii, Lactobacillus murinus, Enterococcus hirae, and microbiota changes within the small intestine
A recent study involving 27 metastatic melanoma patients undergoing immunotherapy found that a higher diversity of the gut microbiome and enrichment of Coprococcus eutactus, Faecalibacterium prausnitzii, Lachnospiraceae bacterium 3 1 46FAA, Prevotella stercorea, Streptococcus anginosus, and Streptococcus sanguinis in pre-treatment stool samples was associated with longer progression-free survival
Summary
Recent advances in cancer treatment and clinical implementation of precision medicine have brought about the improvements in both the disease-free survival and quality of life in cancer patients. As well as clinical studies, suggest the involvement of gut microbiota in cancer initiation and progression through immune system modulation [5]. Growing evidence from preclinical and clinical findings highlights the fact that the host’s microbiome can affect the potential response to different anticancer modalities, mainly chemotherapy and immunotherapy. This leads to the possibility of modulating the gut microbiota to overcome drug resistance, increase the efficacy of cancer treatment, and restore original healthy microbiota [7]. We provide a review of the most recent data related to the emerging role of the microbiome in resistance to anticancer therapies, focusing mainly on chemotherapy and immunotherapy with immune checkpoint inhibitors. We will outline the potential trend for microbiota modulation by probiotics and fecal microbiota transplantation (FMT) to enhance the response to cancer treatment modalities
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