‘Cancer associated fibroblasts’ – more than meets the eye

•‘CAF’ should be conceived as cell ‘state’ rather than a cell type.•Personalized therapy could be extended to the tumor microenvironment.

Cancer associated fibroblasts (CAFs) are a subpopulation of cells that reside within the tumor microenvironment and promotes the transformation process by encouraging tumor growth, angiogenesis, inflammation, and metastasis. CAF-specific proteins serve as both prognostic markers and targets for anticancer drugs. With the growing interest in CAFs, several controversial issues have been raised, including the genomic landscape of these cells, the identity of specific markers, and their cell of origin. Here, we tackle these debated issues and put forward a new definition for ‘CAF’ as a cell ‘state’ rather than a cell type. We hope this conceptualization can resolve the ongoing discrepancies revolving around CAF research and aid in designing better anti-cancer treatment strategies.