Butti Ramesh, Khaladkar Ashwini, Bhardwaj Priya, Prakasam Gopinath
Kidney Cancer Program, Simmons Comprehensive Cancer Centre, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Bombay 400076, India.
Cancer Drug Resist. 2023 Mar 27;6(1):182-204. doi: 10.20517/cdr.2022.72. eCollection 2023.
The context-dependent reciprocal interaction between the cancer cells and surrounding fibroblasts is imperative for regulating malignant potential, metabolic reprogramming, immunosuppression, and ECM deposition. However, recent evidence also suggests that cancer-associated fibroblasts induce chemoresistance in cancer cells to various anticancer regimens. Because of the protumorigenic function of cancer-associated fibroblasts, these stromal cell types have emerged as fascinating therapeutic targets for cancer. However, this notion was recently challenged by studies that targeted cancer-associated fibroblasts and highlighted the underlying heterogeneity by identifying a subset of these cells with tumor-restricting functions. Hence, it is imperative to understand the heterogeneity and heterotypic signaling of cancer-associated fibroblasts to target tumor-promoting signaling processes by sparing tumor-restricting ones. In this review, we discuss the heterogeneity and heterotypic signaling of cancer-associated fibroblasts in shaping drug resistance and also list the cancer-associated fibroblast-targeting therapeutics.
癌细胞与周围成纤维细胞之间的上下文依赖性相互作用对于调节恶性潜能、代谢重编程、免疫抑制和细胞外基质沉积至关重要。然而，最近的证据还表明，癌症相关成纤维细胞会诱导癌细胞对各种抗癌方案产生化学抗性。由于癌症相关成纤维细胞的促肿瘤功能，这些基质细胞类型已成为引人关注的癌症治疗靶点。然而，最近的研究对这一观点提出了挑战，这些研究针对癌症相关成纤维细胞，并通过识别具有肿瘤限制功能的这些细胞亚群突出了潜在的异质性。因此，了解癌症相关成纤维细胞的异质性和异型信号传导，以通过保留具有肿瘤限制功能的信号传导过程来靶向肿瘤促进信号传导过程势在必行。在这篇综述中，我们讨论了癌症相关成纤维细胞在形成耐药性方面的异质性和异型信号传导，并列出了针对癌症相关成纤维细胞的治疗方法。
