Review of Cancer – Associated Fibroblasts and Therapies that Interfere with Their Activity

Received 09 December 2012 Accepted 17 January 2013 Abstract Cancer-associated fibroblasts (CAFs) are a specific but heterogenous population of cells that reside in the tumor microenvironment and play a significant role in the neoplastic process. CAFs participate in tumorigenesis, provide a nurturing environment for neoplastic cells, promote malignant cell growth and invasiveness by remodeling the local extracellular matrix; they have pro-inflammatory and proangiogenic properties. CAFs also confer resistance to chemotherapy and raditation therapy. In order to achieve these activities, CAFs secrete multiple growth factors, cytokines and proteins. Communication between CAFs and malignant cells is not, however, one way; premalignant cells and tumor cells secrete their own cytokines and growth factors that increase CAF numbers and function. There has also been considerable clinical research with agents that may interfere with CAFs but it has been difficult to learn about and measure the interference with CAFs per se. This review addresses the current state of knowledge about CAFs, summarizes the clinical development to date of therapeutics that inhibit CAF growth and function and suggests strategies for future clinical trials that focus particularly on CAFs and their products.