Chemotherapy is one of the most effective methods of systemic cancer treatment. Chemotherapy drugs are delivered through the blood circulation system, and they can act at all stages of the cell cycle, and can target DNA, topoisomerase, or tubulin to prevent the growth and proliferation of cancer cells. However, due to the lack of specific targets for chemotherapeutic agents, there are still unavoidable complications of cytotoxic effects. The effect of the microbiome on human health is clear. There is growing evidence of the potential relationship between the microbiome and the efficacy of cancer therapy. Gut microbiota can regulate the metabolism of drugs in several ways. The presence of bacteria in the tumor environment can also affect the response to cancer therapy by altering the chemical structure of chemotherapeutic agents and affecting their activity and local concentration. However, the underlying mechanisms by which the gut and tumor microbiota affect cancer therapeutic response are unclear. This review provides an overview of the effects of gut and tumor microbiota on the efficacy and adverse effects of chemotherapy in cancer patients, thus facilitating personalized treatment strategies for cancer patients.
Trillions of microbes are present in the human gut. Although the gut microbiota maintains a relatively stable composition throughout the human lifetime, the ratio of different bacteria is affected by the gut microecosystem and changes in the gut microbiota have profound effects on the host (Panebianco et al., 2018a; Liu et al., 2019). Gut microorganisms are involved in a variety of physiological events, including the provision of nutrients and vitamins, the metabolism of drugs and toxicants, the protection of the host from pathogens, the development of the immune system and the maintenance of epithelial mucosal homeostasis, and are important determinants of the physiological or pathological status of the host (Ding et al., 2018; Whisner and Athena Aktipis, 2019; Wong et al., 2019).
Cancer is a globally challenging health problem of human. Despite many advances in cancer treatment, heterogeneous responses and resistance to chemotherapeutic agents remain challenges for cancer treatment. The chemotherapeutic agents lack specific targets, and therefore specific markers and methods for predicting therapeutic efficacy are still lacking.
Effect of gut and tumor microbiota on the antitumor efficacy of chemotherapeutic drugs
Cyclophosphamide is a cell cycle non-specific alkylating agent that acts mainly on the S-phase and exerts cytotoxic effects by affecting DNA synthesis. It is commonly used for the treatment of lymphoma, leukemia, neuroblastoma, and retinoblastoma, as well as ovarian, breast, endometrial, and lung cancers. However, the development of chemotherapy resistance seriously limits its efficacy (Kroemer et al., 2013).
In recent years, it has been shown that gut microbiota is involved in the regulation of the host immune response triggered by Cyclophosphamide. Studies in mouse models have found that Cyclophosphamide could disrupt the intestinal mucus layer, and alter gut microbiota, which was accompanied with the translocation of specific Gram-positive bacteria into secondary lymphoid organs.
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