miRNA-based combinatorial approach for therapeutic efficacy improvement of chemotherapy in relapse and multidrug resistance tumor

MicroRNAs (miRNAs/miRs) are endogenous noncoding RNAs that regulate gene expression at the post-transcriptional level. In cancer biology, microRNAs (miRNAs) have emerged as key regulators of carcinogenesis, progression, and treatment resistance. Due to their ability to modulate multiple oncogenic and tumor-suppressive pathways, they are considered promising diagnostic biomarkers and therapeutic agents. However, despite of significant progress, the clinical translation of miRNA-based biomarkers and therapeutics remains limited due to challenges in stability, delivery, immune activation, and patient-specific responses. Additionally, naked miRNA therapeutics are particularly constrained by rapid degradation and poor bioavailability, underscoring the need for advanced therapeutic strategies including delivery systems. To overcome these limitations, combination therapies involving chemotherapeutic drugs, radiotherapy, immunotherapy, small molecules, antibodies, peptides, and nanotechnology-based formulations have demonstrated enhanced efficacy, reduced drug resistance, and improved therapeutic stability. Preclinical and clinical evidence supports the potential of such combination approaches in amplifying the anti-tumor effects of miRNAs. This chapter highlights the role of miRNAs in cancer initiation and progression, the limitations of miRNA therapies, and the emerging promise of miRNA-based combination therapies. We discuss how miRNA-based combination approaches offer an innovative therapeutic paradigm for effective, patient-friendly, and personalized cancer treatment; however, the need for further in-depth studies are required to optimize their clinical applications.