EMERGING THERAPEUTIC TARGETS WITHIN DNA REPAIR MECHANISMS FOR CANCER TREATMENT STRATEGIES

Abstract

Background: DNA repair mechanisms maintain the genomic integrity, and their deregulation is a typical feature of cancer, providing therapeutic deficiencies that may be leveraged.

Objective: To determine and analyze emerging therapeutic targets in DNA repair pathways, and determine their efficacy in enhancing cancer treatment approaches.

Methodology: A literature review and comparative analysis of homologous recombination (HR)-deficient and HR-proficient cancer cell models were performed in vitro. The cell viability assays, the gene expression profiling, and statistical analysis (p < 0.05) evaluated the drug response to PARP, ATR, and DNA-PK inhibitors.

Findings: PARP inhibition, but not ATR inhibition, decreased viability in HR-deficient cells to about 55% and ATR inhibition alone led to about 60% viability. It is worth mentioning that combination therapy (PARP + ATR inhibitors) showed a synergistic effect, decreasing the cell viability to approximately 35%. Increased expression of PARP1 and ATR was found in tumor cells, in association with greater therapeutic efficacy. They were also found to have resistance mechanisms such as partial restoration of HR functionality.

Conclusion: There is a lot of potential promise behind attacking the DNA repair pathways, especially with combination therapy, to improve the outcomes in cancer treatment. Further studies on synthetic lethality and biomarker-based therapies are needed to progress precision oncology.