Following cetuximab treatment, an upregulation of the transforming growth factor-beta (TGF-beta) signaling pathway was observed in the tumor microenvironment (TME) of CetuximabProg-PDX (the increased tumor volume of patient-derived xenografts), whereas in CetuximabSen-PDXs (the decreased tumor volume of patient-derived xenografts), a downregulation of the same pathway was detected. The stromal TGF-beta signal was found to originate from cancer-associated fibroblasts (CAFs) in the TME; inhibition of TGF-beta, together with cetuximab, succeeded to sensitize CetuximabProg-PDX. The scheme was created with BioRender © 2019.