Dynamic changes in KRASG12/G13-mutated cfDNA in various patients with heavily pretreated KRASG12/G13-mutated advanced cancers. In each panel, the top graph depicts the KRASG12/G13 mutation allelic frequency (MAF) in the wild-type background, and the bottom graph depicts the number of KRASG12/G13 copies per 1 ml of plasma. Red arrows indicate the onset of progressive disease. Shown are sequential measurements of KRASG12/G13 (blue); cancer antigen 125 (CA125) levels (panels A and C), cancer antigen 15-3 (CA15-3) levels (panel B), carcinoembryonic antigen (CEA) levels (panels D–F; orange); and the sum (cm) of target lesions on imaging (grey bars) in (A) a patient with metastatic ovarian carcinoma who received targeted therapy with an ERK inhibitor; (B) a patient with metastatic breast carcinoma who received therapy with an mTOR inhibitor, HDAC inhibitor, and anti-VEGF antibody; (C) a patient with metastatic ovarian carcinoma who received targeted therapy with PI3K and MEK inhibitors; (D) a patient with metastatic ampullary carcinoma who received targeted therapy with a MEK inhibitor.