CHEK2 and melanoma: Notably, the detection of specific mutations exclusively through subsequent ctDNA results, such as ATM mutation in ovarian cancer, TMB-high in gastric cancer, CHEK2 mutation in ovarian cancer, and NRAS mutation in melanoma, led to tumor responses, which exemplifies the potential of longitudinal ctDNA genotyping to uncover novel, actionable targets that may not be evident at the onset of treatment (Fig 6D).