Breast Cancer Drug Resistance: Overcoming the Challenge by Capitalizing on MicroRNA and Tumor Microenvironment Interplay

SIMPLE SUMMARY: The cross-talk between neoplastic cells and microenvironment is known to play a crucial role in tumor development as well as in the phenomenon of resistance to anticancer therapies. MicroRNAs, involved in the pathogenesis of human tumors, are among the molecules exploited in this aberrant cross-talk. Indeed, microRNAs play a crucial function both in the induction of pro-tumoral traits in stromal cells and in the stroma-mediated fueling of tumor aggressiveness. Here, we reviewed the most recent literature concerning the role of miRNAs in shaping the tumor microenvironment, and the consequences on responsiveness to therapies. ABSTRACT: The clinical management of breast cancer reaches new frontiers every day. However, the number of drug resistant cases is still high, and, currently, this constitutes one of the major challenges that cancer research has to face. For instance, 50% of women affected with HER2 positive breast cancer presents or acquires resistance to trastuzumab. Moreover, for patients affected with triple negative breast cancer, standard chemotherapy is still the fist-line therapy, and often patients become resistant to treatments. Tumor microenvironment plays a crucial role in this context. Indeed, cancer-associated stromal cells deliver oncogenic cues to the tumor and vice versa to escape exogenous insults. It is well known that microRNAs are among the molecules exploited in this aberrant crosstalk. Indeed, microRNAs play a crucial function both in the induction of pro-tumoral traits in stromal cells and in the stroma-mediated fueling of tumor aggressiveness. Here, we summarize the most recent literature regarding the involvement of miRNAs in the crosstalk between tumor and stromal cells and their capability to modulate tumor microenvironment characteristics. All up-to-date findings suggest that microRNAs in the TME could serve both to reverse malignant phenotype of stromal cells, modulating response to therapy, and as predictive/prognostic biomarkers.