Unraveling the nexus: Genomic instability and metabolism in cancer
Vaibhavi Gujar, Haojian Li, Tanya T. Paull, Carola A. Neumann, Urbain Weyemi
Abstract
The DNA-damage response (DDR) is a signaling network that enables cells to detect and repair genomic damage. Over the past three decades, inhibiting DDR has proven to be an effective cancer therapeutic strategy. Although cancer drugs targeting DDR have received approval for treating various cancers, tumor cells often develop resistance to these therapies, owing to their ability to undergo energetic metabolic reprogramming. Metabolic intermediates also influence tumor cells' ability to sense oxidative stress, leading to impaired redox metabolism, thus creating redox vulnerabilities. In this review, we summarize recent advances in understanding the crosstalk between DDR and metabolism. We discuss combination therapies that target DDR, metabolism, and redox vulnerabilities in cancer. We also outline potential obstacles in targeting metabolism and propose strategies to overcome these challenges.