Li Chenxin, Qiu Yusong, Zhang Yong
Department of Pathology Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute, Shenyang 110042, China.
Pharmaceuticals (Basel). 2022 Nov 15;15(11):1411. doi: 10.3390/ph15111411.
Non-small cell lung cancer (NSCLC) accounts for most lung cancer cases and is the leading cause of cancer-related deaths worldwide. Treatment options for lung cancer are no longer limited to surgery, radiotherapy, and chemotherapy, as targeted therapy and immunotherapy offer a new hope for patients. However, drug resistance in chemotherapy and targeted therapy, and the low response rates to immunotherapy remain important challenges. Similar to tumor development, drug resistance occurs because of significant effects exerted by the tumor microenvironment (TME) along with cancer cell mutations. Cancer-associated fibroblasts (CAFs) are a key component of the TME and possess multiple functions, including cross-talking with cancer cells, remodeling of the extracellular matrix (ECM), secretion of various cytokines, and promotion of epithelial-mesenchymal transition, which in turn provide support for the growth, invasion, metastasis, and drug resistance of cancer cells. Therefore, CAFs represent valuable therapeutic targets for lung cancer. Herein, we review the latest progress in the use of CAFs as potential targets and mediators of drug resistance for NSCLC treatment. We explored the role of CAFs on the regulation of the TME and surrounding ECM, with particular emphasis on treatment strategies involving combined CAF targeting within the current framework of cancer treatment.
非小细胞肺癌（NSCLC）占大多数肺癌病例，是全球癌症相关死亡的主要原因。肺癌的治疗选择不再局限于手术、放疗和化疗，因为靶向治疗和免疫疗法为患者带来了新的希望。然而，化疗和靶向治疗中的耐药性以及免疫疗法的低反应率仍然是重要挑战。与肿瘤发展类似，耐药性的出现是由于肿瘤微环境（TME）以及癌细胞突变所产生的显著影响。癌症相关成纤维细胞（CAFs）是TME的关键组成部分，具有多种功能，包括与癌细胞相互作用、细胞外基质（ECM）重塑、分泌各种细胞因子以及促进上皮-间质转化，进而为癌细胞的生长、侵袭、转移和耐药性提供支持。因此，CAFs是肺癌有价值的治疗靶点。在此，我们综述了将CAFs作为NSCLC治疗潜在靶点和耐药性介质的最新进展。我们探讨了CAFs在调节TME和周围ECM中的作用，特别强调了在当前癌症治疗框架内涉及联合靶向CAF的治疗策略。
