PURPOSE: There is a clinical need to identify predictive markers of the responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography with computed tomography ((18)FDG-PET/CT) could be a tool of choice for monitoring the early effects of this class of agent on tumor activity. EXPERIMENTAL DESIGN: Using models of human head and neck carcinoma (CAL33 and CAL166 cell lines), we first tested in vitro and in vivo whether the in vivo changes in (18)FDG-PET/CT uptake were associated with the molecular and cellular effects of the EGFR-TKI erlotinib. Then, the pathologic and morphologic changes and the (18)FDG-PET/CT uptake before and after erlotinib exposure in patients were analyzed. RESULTS: Erlotinib strongly inhibited extracellular signal-regulated kinase-1/2 (ERK-1/2) phosphorylation both in the preclinical models and in patients. Western blotting, immunofluorescence, and immunohistochemistry showed that erlotinib did not modify Glut-1 expression at the protein level either in cell line models or in tumor tissue from mouse xenografts or in patients. Phospho-ERK-1/2 inhibition was associated with a reduction in (18)FDG uptake in animal and human tumors. The biological volume was more accurate than the standardized uptake value for the evaluation of the molecular responses. CONCLUSION: These results show that the (18)FDG-PET/CT response is a reliable surrogate marker of the effects of erlotinib in head and neck carcinoma.
PURPOSE: There is a clinical need to identify predictive markers of the responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography with computed tomography ((18)FDG-PET/CT) could be a tool of choice for monitoring the early effects of this class of agent on tumor activity. EXPERIMENTAL DESIGN: Using models of human head and neck carcinoma (CAL33 and CAL166 cell lines), we first tested in vitro and in vivo whether the in vivo changes in (18)FDG-PET/CT uptake were associated with the molecular and cellular effects of the EGFR-TKI erlotinib. Then, the pathologic and morphologic changes and the (18)FDG-PET/CT uptake before and after erlotinib exposure in patients were analyzed. RESULTS:Erlotinib strongly inhibited extracellular signal-regulated kinase-1/2 (ERK-1/2) phosphorylation both in the preclinical models and in patients. Western blotting, immunofluorescence, and immunohistochemistry showed that erlotinib did not modify Glut-1 expression at the protein level either in cell line models or in tumor tissue from mouse xenografts or in patients. Phospho-ERK-1/2 inhibition was associated with a reduction in (18)FDG uptake in animal and humantumors. The biological volume was more accurate than the standardized uptake value for the evaluation of the molecular responses. CONCLUSION: These results show that the (18)FDG-PET/CT response is a reliable surrogate marker of the effects of erlotinib in head and neck carcinoma.
Authors: S Temam; J Spicer; F Farzaneh; J C Soria; D Oppenheim; M McGurk; A Hollebecque; J Sarini; K Hussain; S Soehrman Brossard; L Manenti; S Evers; P Delmar; L Di Scala; C Mancao; F Feuerhake; L Andries; M G Ott; A Passioukov; J P Delord Journal: Ann Oncol Date: 2017-11-01 Impact factor: 32.976
Authors: Vijaya L Damaraju; Maral Aminpour; Michelle Kuzma; Philip Winter; Jordane Preto; Jack Tuszynski; Alexander B J McEwan; Michael B Sawyer Journal: Clin Transl Sci Date: 2021-05-03 Impact factor: 4.689