Accumulating evidence supports not only the functional role of the gut microbiome in cancer development and progression but also its role in defining the efficacy and toxicity of chemotherapeutic agents (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and immunotherapeutic compounds (anti–programmed death-ligand 1/anti–programmed cell death protein 1 and anti–cytotoxic T-lymphocyte-associated antigen 4). This evidence is supported in numerous in vitro, animal, and clinical studies that highlight the importance of microbial mechanisms in defining therapeutic responses. The microbiome therefore shapes oncologic outcomes and is now being leveraged for the development of novel personalized therapeutic approaches in cancer treatment. However, if the microbiome is to be successfully translated into next-generation oncologic treatments, a new multimodal model of the oncomicrobiome must be conceptualized that incorporates gut microbial cometabolism of pharmacologic agents into cancer care. The objective of this review is therefore to outline the current knowledge of oncologic pharmacomicrobiomics and to describe how the multiparametric functions of the gut microbiome influence treatment response across cancer types. The secondary objective is to propose innovative approaches for modulating the gut microbiome in clinical environments that improve therapy efficacy and diminish toxic effects derived from antineoplastic agents for patient benefit.
There is an increasing appreciation that networks of pathobiont microbial drivers play a critical role in the initiation of cancer through a combination of metabolic-, epigenetic-, and immune-mediated pathways

facilitated by the loss of commensal symbionts and their protective homeostatic functions. Moreover, the mucosal ecosystems appear to evolve with disease progression potentiating metastatic potential and even therapeutic resistance.

Even though cancer-microbiome interactions have not yet been fully defined, attention has turned to the therapeutic value of the cancer microbiome in precision cancer care.

Modern oncologic management of most solid cancers requires multimodal therapy, typically consisting of surgery or a combination of cytotoxic and immunologic strategies deployed across increasingly long and diverse patient journeys. The gut “oncomicrobiome” is highly individualized and dynamic in both its structure and function. Under conditions of health, the microbiome possess significant functional plasticity; however, this is diminished during cancer treatment, caused by changes to the diet, the exposome, xenometabolites, and neoadjuvant and adjuvant agents that perturb its structure and function.
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