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Cancer-Associated Fibroblasts: Versatile Players in the Tumor Microenvironment
| Content Provider | MDPI |
|---|---|
| Author | Ganguly, Debolina Chandra, Raghav Karalis, John Teke, Martha Aguilera, Todd Maddipati, Ravikanth Wachsmann, Megan B. Ghersi, Dario Siravegna, Giulia Iii, Herbert Brekken, Rolf Ting, David T. Ligorio, Matteo |
| Copyright Year | 2020 |
| Description | 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 functions. We believe that the development of a unified CAF nomenclature, the standardization of functional assays to assess the loss-of-function of CAF properties, and the establishment of rigorous definitions of CAF subpopulations and their mechanistic functions in cancer progression will be crucial to fully realize the promise of CAF-targeted therapies. |
| Starting Page | 2652 |
| e-ISSN | 20726694 |
| DOI | 10.3390/cancers12092652 |
| Journal | Cancers |
| Issue Number | 9 |
| Volume Number | 12 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2020-09-17 |
| Access Restriction | Open |
| Subject Keyword | Cancers Oncology Cancer-associated Fibroblasts Tumor Microenvironment Heterogeneity Hallmarks of Cancer Chemoresistance Immunomodulation Caf Therapeutics Clinical Trials Targeting Cafs |
| Content Type | Text |
| Resource Type | Article |
