Cancer-Associated Fibroblasts: Implications for Cancer Therapy

SIMPLE SUMMARY: Cancer-associated fibroblasts are important players of the tumour microenvironment. They influence numerous processes during tumour development and progression, including the response of cancer cells to treatment. As a consequence, this cell type has emerged has a prominent target in anti-cancer therapy. In this review, we discuss the function and heterogeneity of fibroblasts as well as their role during treatment. Moreover, we describe how different therapies influence the phenotype of this cell type and the implications of these alterations. Finally, we provide a detailed overview of the current strategies employed in the targeting of fibroblasts as well as future perspectives. We believe that further dissection of the heterogeneity of fibroblasts and of their dynamics, not only during tumour progression, but also in the course of treatment is essential for successful targeting of this cell type and, consequently, for improving patient survival in cancer. ABSTRACT: Tumour cells do not exist as an isolated entity. Instead, they are surrounded by and closely interact with cells of the environment they are emerged in. The tumour microenvironment (TME) is not static and several factors, including cancer cells and therapies, have been described to modulate several of its components. Fibroblasts are key elements of the TME with the capacity to influence tumour progression, invasion and response to therapy, which makes them attractive targets in cancer treatment. In this review, we focus on fibroblasts and their numerous roles in the TME with a special attention to recent findings describing their heterogeneity and role in therapy response. Furthermore, we explore how different therapies can impact these cells and their communication with cancer cells. Finally, we highlight potential strategies targeting this cell type that can be employed for improving patient outcome.