Cancers, Vol. 12, Pages 2652: Cancer-Associated Fibroblasts: Versatile Players in the Tumor Microenvironment

Cancers, Vol. 12, Pages 2652: Cancer-Associated Fibroblasts: Versatile Players in the Tumor Microenvironment Cancers doi: 10.3390/cancers12092652 Authors: Debolina Ganguly Raghav Chandra John Karalis Martha Teke Todd Aguilera Ravikanth Maddipati Megan B. Wachsmann Dario Ghersi Giulia Siravegna Herbert J. Zeh III Rolf Brekken David T. Ting Matteo Ligorio Cancer-associated fibroblasts (CAFs) are indispensable architects of the tumor microenvironment. They perform the essential functions of extracellular matrix deposition, stromal remodeling, tumor vasculature modulation, modification of tumor metabolism, and participation in crosstalk between cancer and immune cells. In this review, we discuss our current understanding of the principal differences between normal fibroblasts and CAFs, the origin of CAFs, their functions, and ultimately, highlight the intimate connection of CAFs to virtually all of the hallmarks of cancer. We address the remarkable degree of functional diversity and phenotypic plasticity displayed by CAFs and strive to stratify CAF biology among different tumor types into practical functional groups. Finally, we summarize the status of recent and ongoing trials of CAF-directed therapies and contend that the paucity of trials resulting in Food and Drug Administration (FDA) approvals thus far is a consequence of the failure to identify targets exclusive of pro-tumorigenic CAF phenotypes that are mechanistically linked to specific CAF...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research