CRISPR/Cas as a tool to overcome drug resistance in cancer: From challenge to opportunity

Drug resistance remains a significant challenge in cancer therapy, often resulting in treatment failure, tumor progression, and metastasis. The underlying resistance mechanisms—including genetic mutations, epigenetic alterations, and modifications in drug efflux pathways—are complex and not yet fully understood. This review explores the application of CRISPR-Cas gene editing technology in understanding and overcoming drug resistance in cancer. It focuses on how CRISPR can identify and target resistance-associated genes to restore drug sensitivity. CRISPR-based approaches enable precise genetic modifications that offer new insights into the molecular basis of drug resistance. The technology has shown promise in dissecting resistance mechanisms and developing targeted therapeutic strategies. Nevertheless, key limitations such as inefficient delivery systems, off-target effects, and limited specificity hinder clinical translation. Current efforts focus on improving guide RNA design, creating more effective delivery vectors, and integrating CRISPR with existing treatments. CRISPR-Cas technology holds significant potential to address drug resistance in cancer by enabling targeted genetic interventions. Continued advancements are required to enhance its safety, specificity, and delivery, paving the way for its integration into future clinical applications. • Gene editing technologies, particularly CRISPR-Cas systems, have played a crucial role in understanding drug resistance mechanisms in cancer. This understanding is vital for developing effective cancer therapies. • Drug resistance remains a significant challenge in cancer treatment, driven by insufficient knowledge of gene functions and regulatory elements. CRISPR-Cas tools aim to address these challenges by studying disease genes, drug resistance mechanisms, and correcting mutations associated with resistance. • Despite its promise, CRISPR-Cas technology faces obstacles such as delivery limitations, low efficiency, specificity issues, and potential off-target effects. Overcoming these challenges is essential to harnessing the full potential of CRISPR-based therapies for combating drug resistance in cancer treatment.