Cancer associated fibroblast mediated chemoresistance: A paradigm shift in understanding the mechanism of tumor progression

One of the undeniable issues with cancer eradication is the evolution of chemoresistance in due course of treatment, and the mechanisms of chemoresistance have been the subject of extensive research for several years. The efficacy of chemotherapy is hindered by cancer epithelium, mostly in a cell-autonomous mechanism. However, recently the valid experimental evidence showed that the surrounding tumor microenvironment (TME) is equivalently responsible for the induction of chemoresistance. Of the verities of cells in the tumor microenvironment, cancer-associated fibroblasts (CAFs) are the major cellular component of TME and act as a key regulator in the acquisition of cancer chemoresistance by providing a protective niche to the cancer cells against the anti-cancer drugs. Moreover, the symbiotic relationship between the tumor and CAFs to obtain key resources such as growth factors and nutrients for optimal tumor growth and proliferation favors the chemoresistance phenotype. Here, in this review, we provide an up-to-date overview of our knowledge of the role of the CAFs in inducing chemoresistance and tumor progression. We also further delineated the emerging events leading to the CAF origins and activation of normal fibroblasts to CAFs. Along with this, we also discuss the novel area of research confined to the CAF targeted therapies of cancer. The identification of CAF-specific markers may allow unveiling new targets and avenues for blunting or reverting the detrimental pro-tumorigenic potential of CAFs in the foreseeable future.