DNA damage and metabolic mechanisms of cancer drug resistance

Cancer drug resistance is one of the main barriers to overcome to ensure durable treatment responses. While many pivotal advances have been made in first combination therapies, then targeted therapies, and now broadening out to immunomodulatory drugs or metabolic targeting compounds, drug resistance is still ultimately universally fatal. In this brief review, we will discuss different strategies that have been used to fight drug resistance from synthetic lethality to tumor microenvironment modulation, focusing on the DNA damage response and tumor metabolism both within tumor cells and their surrounding microenvironment. In this way, with a better understanding of both targetable mutations in combination with the metabolism, smarter drugs may be designed to combat cancer drug resistance.

Automated summary

This review discusses different strategies to combat cancer drug resistance, including synthetic lethality and modulation of the tumor microenvironment. By understanding the relationship between targetable mutations and metabolism in tumor cells and their surrounding microenvironment, smarter drugs can be designed to fight cancer drug resistance.