Exploring the diversity of cancer-associated fibroblasts: insights into mechanisms of drug resistance

Among the various stromal cell types within the tumor microenvironment, cancer-associated fibroblasts (CAFs) emerge as the predominant constituent, exhibiting a diverse array of oncogenic functions not intrinsic to normal fibroblasts. Their involvement spans across all stages of tumorigenesis, encompassing initiation, progression, and metastasis. Current understanding posits the coexistence of distinct subpopulations of CAFs within the tumor microenvironment across a spectrum of solid tumors, showcasing both pro- and antitumor activities. Recent advancements in single-cell transcriptomics have revolutionized our ability to meticulously dissect the heterogeneity inherent to CAF populations. Furthermore, accumulating evidence underscores the pivotal role of CAFs in conferring therapeutic resistance to tumors against various drug modalities. Consequently, efforts are underway to develop pharmacological agents specifically targeting CAFs. This review embarks on a comprehensive analysis, consolidating data from 36 independent single-cell RNA sequencing investigations spanning 17 distinct human malignant tumor types. Our exploration centers on elucidating CAF population markers, discerning their prognostic relevance, delineating their functional contributions, and elucidating the underlying mechanisms orchestrating chemoresistance. Finally, we deliberate on the therapeutic potential of harnessing CAFs as promising targets for intervention strategies in clinical oncology.