The transformation of cancer-associated fibroblasts: Current perspectives on the role of TGF-β in CAF mediated tumor progression and therapeutic resistance

Over the last few years, the Transforming growth factor-beta (TGF-beta) has been significantly considered as an effective and ubiquitous mediator of cell growth. The cytokine, TGF-beta 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-beta 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-beta to induce the malignant progression. Here in this review, we have dissected the most recent advancements in understanding the mechanisms of TGF-beta induced CAF activation, their multiple origins, and most importantly their role in conferring chemoresistance. Considering the pivotal role of TGF-beta in tumor pemgression and associated stemness, it is one the proven clinical targets We have also included the clinical trials going on, targeting the TGF-beta 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.

Automated summary

TGF-beta is considered as a crucial mediator of cell growth and cancer cell progression through both SMAD-dependent and independent pathways. In the tumor microenvironment, cancer-associated fibroblasts (CAFs) play a prominent role in tumor progression and chemoresistance, with TGF-beta facilitating the crosstalk between CAFs and tumor cells. Targeting the TGF-beta and CAFs interaction in clinical trials is essential for developing successful anti-cancer therapies.