Over the last few years, the Transforming growth factor- β (TGF-β) has been significantly considered as an effective and ubiquitous mediator of cell growth. The cytokine, TGF-β is being increasingly recognized as the most potent inducer of cancer cell initiation, differentiation, migration as well as progression through both the SMAD-dependent and independent pathways. There is growing evidence that supports the role of secretory cytokine TGF-β as a crucial mediator of tumor-stroma crosstalk. Contextually, the CAFs are the prominent component of tumor stroma that helps in tumor progression and onset of chemoresistance. The interplay between the CAFs and the tumor cells through the paracrine signals is facilitated by cytokine TGF-β to induce the malignant progression. Here in this review, we have dissected the most recent advancements in understanding the mechanisms of TGF-β induced CAF activation, their multiple origins, and most importantly their role in conferring chemoresistance. Considering the pivotal role of TGF-β in tumor perogression and associated stemness, it is one the proven clinical targets We have also included the clinical trials going on, targeting the TGF-β and CAFs crosstalk with the tumor cells. Ultimately, we have underscored some of the outstanding issues that must be deciphered with utmost importance to unravel the successful strategies of anti-cancer therapies.

在过去几年中，转化生长因子-β (TGF-β) 已被广泛认为是一种有效且普遍存在的细胞生长介质。细胞因子 TGF-β 越来越被认为是癌细胞通过 SMAD 依赖和独立途径启动、分化、迁移以及进展的最有效诱导剂。越来越多的证据支持分泌细胞因子 TGF-β 作为肿瘤-基质串扰的关键介质的作用。在上下文中，CAF 是肿瘤基质的重要组成部分，有助于肿瘤进展和化学抗性的发生。细胞因子 TGF-β 促进了 CAF 和肿瘤细胞之间通过旁分泌信号的相互作用，从而诱导恶性进展。在这篇评论中，我们剖析了了解 TGF-β 诱导的 CAF 激活机制、它们的多种起源以及最重要的是它们在赋予化学抗性中的作用方面的最新进展。考虑到 TGF-β 在肿瘤进展和相关干性中的关键作用，它是经过验证的临床靶标之一。我们还包括正在进行的临床试验，针对 TGF-β 和 CAFs 与肿瘤细胞的串扰。最后，我们强调了一些必须破译的突出问题，以揭示抗癌治疗的成功策略。它是经过验证的临床靶点之一 我们还包括正在进行的临床试验，针对 TGF-β 和 CAFs 与肿瘤细胞的串扰。最后，我们强调了一些必须破译的突出问题，以揭示抗癌治疗的成功策略。它是经过验证的临床靶点之一 我们还包括正在进行的临床试验，针对 TGF-β 和 CAFs 与肿瘤细胞的串扰。最后，我们强调了一些必须破译的突出问题，以揭示抗癌治疗的成功策略。