Luan Siyuan, Zeng Xiaoxi, Zhang Chao, Qiu Jiajun, Yang Yushang, Mao Chengyi, Xiao Xin, Zhou Jianfeng, Zhang Yonggang, Yuan Yong
Department of Thoracic Surgery, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China.
Front Cell Dev Biol. 2021 Mar 19;9:664816. doi: 10.3389/fcell.2021.664816. eCollection 2021.
Drug resistance represents the major obstacle to get the maximum therapeutic benefit for patients with esophageal cancer since numerous patients are inherently or adaptively resistant to therapeutic agents. Notably, increasing evidence has demonstrated that drug resistance is closely related to the crosstalk between tumor cells and the tumor microenvironment (TME). TME is a dynamic and ever-changing complex biological network whose diverse cellular and non-cellular components influence hallmarks and fates of tumor cells from the outside, and this is responsible for the development of resistance to conventional therapeutic agents to some extent. Indeed, the formation of drug resistance in esophageal cancer should be considered as a multifactorial process involving not only cancer cells themselves but cancer stem cells, tumor-associated stromal cells, hypoxia, soluble factors, extracellular vesicles, . Accordingly, combination therapy targeting tumor cells and tumor-favorable microenvironment represents a promising strategy to address drug resistance and get better therapeutic responses for patients with esophageal cancer. In this review, we mainly focus our discussion on molecular mechanisms that underlie the role of TME in drug resistance in esophageal cancer. We also discuss the opportunities and challenges for therapeutically targeting tumor-favorable microenvironment, such as membrane proteins, pivotal signaling pathways, and cytokines, to attenuate drug resistance in esophageal cancer.
耐药性是食管癌患者获得最大治疗益处的主要障碍，因为许多患者对治疗药物具有固有或适应性耐药性。值得注意的是，越来越多的证据表明，耐药性与肿瘤细胞和肿瘤微环境（TME）之间的相互作用密切相关。肿瘤微环境是一个动态且不断变化的复杂生物网络，其多样的细胞和非细胞成分从外部影响肿瘤细胞的特征和命运，这在一定程度上导致了对传统治疗药物的耐药性产生。事实上，食管癌中耐药性的形成应被视为一个多因素过程，不仅涉及癌细胞本身，还涉及癌症干细胞、肿瘤相关基质细胞、缺氧、可溶性因子、细胞外囊泡等。因此，针对肿瘤细胞和有利于肿瘤生长的微环境的联合治疗是解决耐药性问题并为食管癌患者获得更好治疗反应的一种有前景的策略。在本综述中，我们主要集中讨论肿瘤微环境在食管癌耐药中作用的分子机制。我们还讨论了靶向有利于肿瘤生长的微环境（如膜蛋白、关键信号通路和细胞因子）以减轻食管癌耐药性的治疗机会和挑战。
