Translational Aspects of DNA Damage Repair in Optimizing Cancer Chemotherapy

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• The DNA Damage Repair (DDR) pathway is critical for regulating chemotherapy efficacy.
• Understanding DDR mechanisms is vital for advancing precision oncology.

Purpose of the Study:

• To systematically review DDR pathways in mediating chemotherapy resistance.
• To elucidate correlations between DDR molecular events and chemotherapy sensitivity.
• To explore novel therapeutic strategies targeting DDR.

Main Methods:

• Systematic analysis of five core DDR pathways (HRR, NHEJ, BER, NER, MMR).
• Elucidation of molecular events like BRCA1/2 deficiency, MMR abnormalities, and ATM/ATR dysregulation.
• Integration of multi-omics data for biomarker system development.

Main Results:

• DDR deficiency biomarkers predict platinum-based drug efficacy.
• PARP inhibitors reverse HRR-deficient tumor resistance via synthetic lethality.
• ATM/ATR inhibitors show synergistic effects with chemotherapy.
• DDR deficiency enhances immunotherapy response through neoantigen release.

Conclusions:

• Targeting DDR pathways offers innovative strategies to overcome chemotherapy resistance.
• DDR pathway assessment via multi-dimensional biomarkers enables personalized treatment.
• Synergistic combinations of DDR inhibitors with other therapies hold promise for cancer treatment.