The functional dichotomy of exosomal microRNAs in TNBC: implications for chemoresistance and integrated theranostics

Triple Negative Breast Cancer (TNBC) is an oncological challenge and notorious for its aggressiveness, chemoresistance and recurrence in patients. Its treatment can be complex and unpredictable due to its varied genomic profile and development of non-responsiveness to many treatment regimens. It also adds to the socio-economic burden. The hunt for new diagnostic and therapeutic angles has led to one of the most important discoveries of the past few decades - exosomal microRNAs. Enclosed within nanoscale vesicles, these non-coding regulatory RNAs are central players in intercellular communication, driving cancer progression and governing the immune system. Tumor-originating exosomes, dubbed as Oncosomes, are unusually large and carry potent, pro-oncogenic oncomiRs. These oncogenic exosomal cargo arising from resistant cells can provoke the same effects in sensitive cells through a myriad of mechanisms such as post-transcriptional pathway regulation, DNA repair modification, tumor environment crosstalk, transporter-mediated drug efflux, metabolic reprogramming, and more. Ultimately, exosomal miRNAs can be a double-edged sword as their dysregulation exacerbates the disease, yet their unique properties make them ideal candidates as diagnostic biomarkers and a versatile therapeutic modality. This review specifically provides a unique and in-depth view of the multifaceted involvement of exosomal microRNAs in TNBC chemoresistance while also highlighting recent literature evidence that encompasses their varied and profound potential as tools to overcome this very phenomenon.