癌症治疗中抗药性是一个重要的挑战之一。一般来说，重点放在遗传驱动因子上，尤其是治疗抗药性的遗传突变。然而，非突变机制，如表观遗传修饰以及由癌细胞可塑性驱动的肿瘤微环境（TME）改变，也参与了治疗抗药性。可塑性的概念主要依赖于非癌干细胞（CSCs）向CSCs的转化，或经不同机制和各种信号通路的上皮间质转化。癌细胞可塑性在治疗抗药性中起着关键作用，因为癌细胞能够通过改变表型逃脱治疗，从而增强肿瘤的进展。新的证据表明，肠道微生物能够通过影响与癌细胞可塑性相关的机制来改变癌细胞特性。有趣的是，肠道微生物还可以通过调节与癌细胞可塑性相关的机制来影响抗癌药物的治疗效果。肠道微生物已被证明能够减少某些临床药物的毒性。在这里，我们记录了肠道微生物在改变癌症可塑性方面对现有抗癌药物的治疗效果起到的关键作用。因此，对于肠道微生物在癌细胞可塑性中新兴作用的更多了解，可以帮助开发基于肠道微生物的新型治疗方法，以克服抗药性或降低现有药物的毒性。此外，为了提高治疗的有效性，有必要进行更多的临床和临床前研究，以充分理解肠道微生物的机制。© 2023. 作者，独家授权给 Springer Science+Business Media, LLC，Springer Nature的一部分。

Resistance to therapeutic agents is one of the major challenges in cancer therapy. Generally, the focus is given to the genetic driver, especially the genetic mutation behind the therapeutic resistance. However, non-mutational mechanisms, such as epigenetic modifications, and TME alteration, which is mainly driven by cancer cell plasticity, are also involved in therapeutic resistance. The concept of plasticity mainly relies on the conversion of non-cancer stem cells (CSCs) to CSCs or epithelial-to-mesenchymal transition via different mechanisms and various signaling pathways. Cancer plasticity plays a crucial role in therapeutic resistance as cancer cells are able to escape from therapeutics by shifting the phenotype and thereby enhancing tumor progression. New evidence suggests that gut microbiota can change cancer cell characteristics by impacting the mechanisms involved in cancer plasticity. Interestingly, gut microbiota can also influence the therapeutic efficacy of anticancer drugs by modulating the mechanisms involved in cancer cell plasticity. The gut microbiota has been shown to reduce the toxicity of certain clinical drugs. Here, we have documented the critical role of the gut microbiota on the therapeutic efficacy of existing anticancer drugs by altering the cancer plasticity. Hence, the extended knowledge of the emerging role of gut microbiota in cancer cell plasticity can help to develop gut microbiota-based novel therapeutics to overcome the resistance or reduce the toxicity of existing drugs. Furthermore, to improve the effectiveness of therapy, it is necessary to conduct more clinical and preclinical research to fully comprehend the mechanisms of gut microbiota.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.