DNA damage may result from both endogenous factors (e.g., replication errors, oxidative deamination, and reactive oxygen species) and exogenous factors (e.g., UV light and radiation). The processes of DNA repair involve the identification of DNA damage and subsequent restoration by several processes including nucleotide excision repair, base excision repair, non-homologous-end-joining, and homologous recombination depending on the type of DNA damage (single stranded DNA break vs. double stranded DNA break. If damage to DNA cannot be repaired, the cell will undergo cell cycle arrest, senescence, or programmed cell death. 
Figure 1. The cell signaling pathways that are involved in DNA damage are displayed. Excision repair cross-complementation group genes (ERCC-1/-4), X-ray repair complementing defective repair in Chinese hamster cells genes (XRCC-1/-5/-6), poly(ADP-ribose) polymerase 1 (PARP1), the Fanconi anemia gene complex (FANC-A/-C/-D2/-E/-F/-G/-L), Rad51 recombinase (RAD51), ATM serine/threonine kinase (ATM), ATR serine/threonine kinase (ATR), protein kinase, DNA-activated catalytic polypeptide (PRKDC), and the breast cancer, early onset genes (BRCA1/2) are included in the DNA damage pathway. Specific nodes in the pathway that are therapeutically actionable are noted.
MLH1, BRCA1, and BRCA2 are the most frequent biomarkers that serve as inclusion criteria in therapies targeting the DNA damage/repair pathway.
Biomarkers in the DNA damage/repair pathway serve as inclusion eligibility criteria in 273 clinical trials, of which 253 are open and 20 are closed. The genes BRCA1, BRCA2, MLH1, NPM1, and ATM on this pathway most frequently harbor alterations that are inclusion eligibility criteria for clinical trials.
Of the trials that contain alteration(s) in the DNA damage/repair pathway as inclusion criteria, 2 are early phase 1 (2 open), 4 are n/a (4 open), 62 are phase 1 (57 open), 38 are phase 1/phase 2 (36 open), 133 are phase 2 (121 open), 7 are phase 2/phase 3 (7 open), 26 are phase 3 (25 open), and 1 is phase 4 (1 open) .