Patient derived xenograft (PDX) models – which utilize tissues or cells from patients for in vivo tumor studies – are used to study antitumor activity and mechanisms of intrinsic and acquired resistance, but it is unclear how well they translate to clinical responses. To address this, researchers led by Funda Meric-Bernstam, M.D., developed PDX models in a co-clinical trial to compare against patient responses with the bispecific HER-2 targeted antibody zanidatamab. Of 36 tumors implanted, the researchers established 19 models from 17 patients with a broad range of HER2-expressing cancers.
In vivo testing showed the PDXs accurately reflected the tumor characteristics and antitumor activity of their matched patients in seven of eight co-clinical models. Additionally, the researchers identified amplification of MET and MYC genes as a potential mechanism of zanidatamab resistance, showing that MET inhibitors enhanced zanidatamab both in vitro and in vivo. This study provides evidence that PDXs established from biopsies in clinical trials are a powerful translational research tool, providing further insights for developing therapeutic strategies.