Wu Peijie, Gao Wei, Su Miao, Nice Edouard C, Zhang Wenhui, Lin Jie, Xie Na
School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
Front Cell Dev Biol. 2021 Mar 1;9:641469. doi: 10.3389/fcell.2021.641469. eCollection 2021.
Cancer is a disease which frequently has a poor prognosis. Although multiple therapeutic strategies have been developed for various cancers, including chemotherapy, radiotherapy, and immunotherapy, resistance to these treatments frequently impedes the clinical outcomes. Besides the active resistance driven by genetic and epigenetic alterations in tumor cells, the tumor microenvironment (TME) has also been reported to be a crucial regulator in tumorigenesis, progression, and resistance. Here, we propose that the adaptive mechanisms of tumor resistance are closely connected with the TME rather than depending on non-cell-autonomous changes in response to clinical treatment. Although the comprehensive understanding of adaptive mechanisms driven by the TME need further investigation to fully elucidate the mechanisms of tumor therapeutic resistance, many clinical treatments targeting the TME have been successful. In this review, we report on recent advances concerning the molecular events and important factors involved in the TME, particularly focusing on the contributions of the TME to adaptive resistance, and provide insights into potential therapeutic methods or translational medicine targeting the TME to overcome resistance to therapy in clinical treatment.
癌症是一种预后通常较差的疾病。尽管已经针对各种癌症开发了多种治疗策略，包括化疗、放疗和免疫疗法，但对这些治疗的耐药性常常阻碍临床疗效。除了肿瘤细胞中由基因和表观遗传改变驱动的主动耐药外，肿瘤微环境（TME）也被报道是肿瘤发生、进展和耐药中的关键调节因子。在此，我们提出肿瘤耐药的适应性机制与TME密切相关，而不是依赖于对临床治疗的非细胞自主性变化。尽管对由TME驱动的适应性机制的全面理解需要进一步研究以充分阐明肿瘤治疗耐药的机制，但许多针对TME的临床治疗已经取得成功。在本综述中，我们报告了关于TME中涉及的分子事件和重要因素的最新进展，特别关注TME对适应性耐药的贡献，并提供针对TME的潜在治疗方法或转化医学的见解，以克服临床治疗中的治疗耐药性。
