Carcinoma-associated fibroblasts (CAFs) are activated fibroblasts during
development of several cancer types, and therefore emerge as an attractive therapeutic
target for cancer therapy. Drugs such as PT-100 and sibrotuzumab that block the
functions of CAFs have already been in clinical trials. However, these drugs exhibit
limited efficacy in patients, partially due to the fact that currently used biomarkers for
determining efficacy are not CAF-specific. Furthermore, depletion of CAFs may promote
carcinogenesis and accelerate cancer progression by inducing immunosuppression and
hypoxia, leading to reduced survival. Accumulating evidence demonstrates that restoring
the expression of key microRNA induces the functional conversion of CAFs into normal
fibroblasts by targeting different signaling pathways and metabolic mechanisms.
Therefore, reprograming CAFs into normal fibroblasts by altering specific expression of
microRNAs, rather than targeted ablation, may be an effective, novel strategy for cancer
treatment. This review focuses on specific microRNAs involved in the transformation of
CAFs as well as their multiple roles during tumorigenesis and chemo-resistance.