Heterotypic signaling of cancer-associated fibroblasts in shaping the cancer cell drug resistance.

IF 4.6 Q1 ONCOLOGY 癌症耐药(英文) Pub Date : 2023-03-27 eCollection Date: 2023-01-01 DOI:10.20517/cdr.2022.72
Ramesh Butti, Ashwini Khaladkar, Priya Bhardwaj, Gopinath Prakasam
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Abstract

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.

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癌症相关成纤维细胞的异型信号形成了癌细胞的抗药性。
癌细胞与周围成纤维细胞之间的相互影响是调节恶性潜能、代谢重编程、免疫抑制和 ECM 沉积的必要条件。然而,最近的证据也表明,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疗抵抗。由于癌症相关成纤维细胞具有原发性致癌功能,这些基质细胞类型已成为令人着迷的癌症治疗靶点。然而,最近一些针对癌症相关成纤维细胞的研究对这一观点提出了挑战,这些研究通过鉴定这些细胞中具有肿瘤抑制功能的亚群,突出了潜在的异质性。因此,当务之急是了解癌症相关成纤维细胞的异质性和异型信号转导,以针对促进肿瘤的信号转导过程,同时避免抑制肿瘤的信号转导过程。在这篇综述中,我们将讨论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转导,并列举癌症相关成纤维细胞靶向疗法。
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