Fig. 1

Anti-tumor activity profile of cetuximab in a randomized population-level PDX clinical trial in HNSCCs. a Workflow for the randomized PCT of cetuximab. Drug response phenotypes were assigned as “sensitive”, “acquired resistance”, or “intrinsic resistance” based upon the tumor volume change. Twenty-one days after the first-round treatment initiation, mPD cases were classified into the intrinsic resistance group. mCR cases that did not relapse within 90 days after the first-round treatment initiation were classified into the sensitive group. Relapsed cases were classified into the acquired resistance group if they had an mPD phenotype in the third week after the second drug treatment initiation. b Waterfall plot of the PDX average response to cetuximab, defined as tumor volume change compared with tumor volume at baseline (Day0); each bar represents an individual PDX (n = 49). Dotted lines indicate the cutoff values for arbitrarily defined categories of therapy response, as follows: intrinsic resistance (dark blue), acquired resistance (blue), sensitive (dark brown), reversible drug-tolerant persister (light green); individual differences (light aquamarine), short observation time (light grey). The x axis represents each case, and the y axis represents the tumor volume change. The maximum threshold for tumor volume change was set at 200%. The minimum threshold for tumor volume change was set at −100%. The pie chart at the top right shows the distribution (as proportions) of the different cetuximab-response groups (n = 49). c, d Representative tumor volume growth curve in 49 cases of PDXs treated with cetuximab. Tumor volume growth curve for the sensitive and intrinsic resistance groups (c) and the acquired drug resistance group (d). e Representation of PDXs versus patient responses for the 6 cases in our PCT. The size of the circles represents the number of subjects in each response category. f Tumor growth of PDX_489 treated with cetuximab and PBS as single agents. g CT scans showing the anti-EGFR monoclonal antibody response of patient HNSCC_489. h Tumor growth of PDX_545 treated with cetuximab and PBS as single agents. i CT scans showing the anti-EGFR monoclonal antibody response of patient HNSCC_545. Yellow circles indicate the tumor localization