Cancer-Associated Fibroblasts: Versatile Players in the Tumor Microenvironment
Division of Surgical Oncology, Department of Surgery, UT Southwestern (University of Texas Southwestern Medical Center), Dallas, TX 75390, USA
Department of Radiation Oncology, UT Southwestern (University of Texas Southwestern Medical Center), Dallas, TX 75390, USA
Harold C. Simmons Comprehensive Cancer Center, UT Southwestern (University of Texas Southwestern Medical Center), Dallas, TX 75390, USA
Department of Internal Medicine, UT Southwestern (University of Texas Southwestern Medical Center), Dallas, TX 75390, USA
Department of Pathology, Veterans Affairs North Texas Health Care System, Dallas, TX 75216, USA
College of Information Science & Technology, University of Nebraska at Omaha, Omaha, NE 68182, USA
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 22 August 2020 / Revised: 11 September 2020 / Accepted: 13 September 2020 / Published: 17 September 2020
Cancer-associated fibroblasts (CAFs) are key players in the tumor microenvironment. They are responsible for potentiating growth and metastasis through versatile functions, including maintenance of the extracellular matrix, blood vessel formation, modulation of tumor metabolism, suppression of antitumor immunity, and promotion of chemotherapy resistance. As such, CAFs are associated with poor prognosis and have emerged as a focus of anticancer research. In this review, we discuss the origins of CAFs, their heterogenous subtypes and their properties. We then detail the current state of preclinical and clinical research targeting CAF activities. We believe the limited efficacy of current cancer therapeutic approaches is driven by an incomplete understanding of CAF functions and by a nonstandardized CAF classification system. Therefore, we suggest a unified CAF classification based on specific functions to develop a new class of therapies that will focus on targeting the pro-tumorigenic properties of CAFs during tumor progression.