The role of synthetic lethality in overcoming cancer therapy resistance: Emerging paradigm and recent advances.

Abstract

Cancer therapy resistance remains a major barrier to successful treatment, often leading to reduced clinical efficacy or cancer relapse. Synthetic lethality (SL) has emerged as a promising strategy to exploit genetic vulnerabilities in cancer cells, allowing for more selective and less toxic therapies. By leveraging the genetic or non-genetic adaptations that cancer cells develop under therapeutic pressure, SL-based therapies provide a more precise and less toxic treatment approach. Additionally, SL-driven drug combinations not only delay development of drug resistance but also enhance therapeutic efficacy, representing a transformative shift in cancer management. A comprehensive understanding of SL mechanisms in the context of drug resistance is essential for advancing effective treatment strategies. This review highlights recent advances in SL research, emphasizing the gene screening techniques in overcoming cancer therapy resistance.