Unraveling the nexus: Genomic instability and metabolism in cancer

Area of Science:

• Oncology
• Molecular Biology
• Metabolic Engineering

Background:

• The DNA-damage response (DDR) is crucial for genomic stability and a validated cancer therapeutic target.
• Cancer cells develop resistance to DDR inhibitors through metabolic reprogramming, impacting redox balance.
• Metabolic intermediates influence oxidative stress sensing and redox metabolism in tumors.

Purpose of the Study:

• To review recent advances in the interplay between DDR and cellular metabolism.
• To discuss combination therapies targeting DDR, metabolism, and redox vulnerabilities in cancer.
• To identify challenges and propose strategies for targeting cancer metabolism.

Main Methods:

• Literature review of recent research on DDR, cancer metabolism, and redox biology.
• Analysis of preclinical and clinical studies on combination therapies.
• Synthesis of findings to propose therapeutic strategies.

Main Results:

• Metabolic reprogramming is a key mechanism of resistance to DDR-targeted cancer therapies.
• Targeting metabolic pathways can exploit redox vulnerabilities in cancer cells.
• Combination strategies involving DDR inhibitors, metabolic modulators, and redox agents show promise.

Conclusions:

• The crosstalk between DDR and metabolism presents significant therapeutic opportunities.
• Overcoming resistance requires integrated approaches targeting multiple cellular pathways.
• Further research into metabolic vulnerabilities is essential for effective cancer treatment.