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Therapeutic targeting of DNA repair pathway dysregulation in aging, cancer, and neurodegeneration - PubMed

4 hours ago
  • #therapeutic targeting
  • #aging cancer neurodegeneration
  • #DNA repair
  • Genome maintenance is a key vulnerability in aging, cancer, and neurodegeneration, with therapeutic implications of DNA repair dysregulation still not fully understood.
  • The review covers dysregulation in multiple DNA repair pathways (base excision, nucleotide excision, mismatch, homologous recombination, non-homologous end joining) and drivers like oxidative stress and telomere dysfunction.
  • In aging and neurodegeneration, repair defects lead to senescence and inflammation; in cancer, tumor cells rewire repair for survival and resistance.
  • Biomarkers for repair states and emerging therapies targeting molecules such as PARP, ATR, ATM, DNA-PK, POLQ, and cGAS-STING are summarized.
  • Clinical success depends on context-specific repair states and dependencies, enabling tailored treatments to restore repair in aging/neurodegeneration or exploit repair addiction in cancer.