MicroRNA biomarkers for predicting treatment response and resistance to bevacizumab in cancer

Abstract

Bevacizumab (Avastin), a pioneering FDA-approved humanized monoclonal antibody, functions as an antiangiogenic agent by selectively binding to all soluble isoforms of vascular endothelial growth factor-A (VEGF-A), thereby inhibiting VEGF-A receptor (VGFR) interactions on endothelial cells and disrupting critical signaling pathways for neovascularization. Preclinical in vivo studies have demonstrated that bevacizumab effectively suppresses new blood vessel formation, induces regression of immature tumor vasculature, and transiently normalizes surviving vessels, which enhances the delivery and efficacy of cytotoxic chemotherapy. Additionally, bevacizumab may exert direct antitumor effects through modulation of VEGF-A-mediated signaling pathways in malignant cells. Despite these therapeutic benefits, drug resistance remains a formidable barrier to successful cancer treatment, often resulting from complex metabolic and enzymatic alterations in tumor cells. MicroRNAs (miRNAs), small non-coding RNA (ncRNA) molecules, that regulate gene expression post-transcriptionally, have emerged as critical modulators of oncogenesis or tumor suppression by influencing processes such as inflammation, cell cycle progression, apoptosis, metastasis, and angiogenesis. Dysregulation of miRNA expression is closely linked to cancer initiation, progression, and therapeutic response. Recent evidence highlights distinct miRNA expression profiles between bevacizumab responders and non-responders, with specific miRNAs, such as miR-92b-3p, miR-10a-5p, miR-125a-5p, etc. being upregulated in patients exhibiting favorable responses. In this framework, the current review underscores the pivotal role of miRNAs in modulating cancer therapy outcomes and advocates for further research into miRNA profiling as a predictive tool to overcome drug resistance and optimize bevacizumab efficacy. Integrating miRNA analysis into clinical practice holds promise for advancing personalized cancer treatment and improving patient prognosis.