Cancer-associated fibroblasts: from basic science to anticancer therapy

Abstract

Cancer-associated fibroblasts (CAFs), as a central component of the tumor microenvironment in primary and metastatic tumors, profoundly influence the behavior of cancer cells and are involved in cancer progression through extensive interactions with cancer cells and other stromal cells. Furthermore, the innate versatility and plasticity of CAFs allow their education by cancer cells, resulting in dynamic alterations in stromal fibroblast populations in a context-dependent manner, which highlights the importance of precise assessment of CAF phenotypical and functional heterogeneity. In this review, we summarize the proposed origins and heterogeneity of CAFs as well as the molecular mechanisms regulating the diversity of CAF subpopulations. We also discuss current strategies to selectively target tumor-promoting CAFs, providing insights and perspectives for future research and clinical studies involving stromal targeting.

Cancer: Reprogramming cells that support tumors

Tumors reprogram nearby wound-healing cells into cancer-associated fibroblasts (CAFs) to support their metabolism, escape the immune response and develop resistance to chemotherapy; targeting CAFs may provide therapeutic opportunities. CAFs are very diverse, and their origins and specific roles are not well understood. New genetic tools allow precise profiling of CAFs and their functions, and Dakai Yang at Jiangsu University in Zhenjiang, China, and co-workers have reviewed CAF diversity and the mechanisms by which they are generated. Although most CAFs support tumors, some CAFs fight tumors, and they can potentially be converted from one form to another. Improving our understanding of the variety of CAFs, their functions, and how they interact with tumor cells may help in identifying tumor-suppressing CAFs and in developing precision medicine treatments for various types of cancer.