Critical functions of Notch signaling pathways in the development of cancer drug resistance

The Notch signaling pathway is widely recognized as a major driver of cancer drug resistance, influencing diverse cellular processes that collectively undermine the effectiveness of cancer therapies. This review delivers an in-depth overview of the molecular mechanisms through which Notch signaling governs drug resistance in cancer. Key areas discussed include apoptosis, DNA damage response and repair, non-coding RNAs (ncRNAs), and cancer stem cells, all of which interact with Notch signaling to mediate resistance. Additionally, the roles of drug metabolism and transporters in conjunction with Notch signaling are explored. We delve into how the pathway influences cancer pathogenesis and its implications for treatment, focusing on the therapeutic potential of targeting Notch signaling to overcome resistance. Special attention is given to Notch’s involvement in apoptosis regulation, DNA damage repair, additionally, it plays a pivotal role in preserving cancer stem cells and greatly impacts drug metabolism and transporter activity. The review concludes with a discussion on the clinical implications of targeting Notch signaling in cancer therapy, providing insights into future directions for improving patient outcomes and developing more effective treatment strategies.