Abstract
Overexpression of the human epidermal growth factor receptor (HER) family and their ligands plays an important role in many cancers. Targeting multiple members of the HER family simultaneously may increase the therapeutic efficacy. Here, we report the ability to image the therapeutic response obtained by targeting HER family members individually or simultaneously using the novel monoclonal antibody (mAb) mixture Pan-HER. Mice with subcutaneous BxPC-3 pancreatic adenocarcinomas were divided into five groups receiving vehicle or mAb mixtures directed against either EGFR (HER1), HER2, HER3 or all three receptors combined by Pan-HER. Small animal positron emission tomography/computed tomography (PET/CT) with 2'-deoxy-2'-[(18)F]fluoro-D-glucose (FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) was performed at baseline and at day 1 or 2 after initiation of therapy. Changes in tumor uptake of tracers were quantified and compared to reduction in tumor size. Imaging results were further validated by immunohistochemistry and qPCR. Mean FDG and FLT uptake in the Pan-HER treated group decreased by 19 ± 4.3% and 24 ± 3.1%, respectively. The early change in FDG and FLT uptake correlated with tumor growth at day 23 relative to day 0. Ex vivo molecular analyses of markers associated with the mechanisms of FDG and FLT uptake confirmed the in vivo imaging results. Taken together, the study supports the use of FDG and FLT as imaging biomarkers of early response to Pan-HER therapy. FDG and FLT PET/CT imaging should be considered as imaging biomarkers in clinical evaluation of the Pan-HER mAb mixture.
Highlights
Dysregulation and overexpression of the human epidermal growth factor receptor (HER) family and their ligands play an important role in many cancers
Taken together, the study supports the use of FDG and FLT as imaging biomarkers of early response to Pan-HER therapy
FDG and FLT Positron emission tomography (PET)/computed tomography (CT) imaging should be considered as imaging biomarkers in clinical evaluation of the Pan-HER monoclonal antibodies (mAb) mixture
Summary
Dysregulation and overexpression of the human epidermal growth factor receptor (HER) family and their ligands play an important role in many cancers. The HER family consists of four members: EGFR/HER1, ErbB2/HER2, ErbB-3/HER3, and ErbB-4/HER4. Approved cancer treatments based on monoclonal antibodies (mAb) target receptors individually. It has recently been shown that simultaneously targeting EGFR, HER2, and HER3 with a Pan-HER (mAb) mixture consisting of two EGFR-, two HER2- and two HER3-targeting mAbs with non-overlapping epitopes in a single drug compound increases the therapeutic efficacy compared with targeting the receptors individually [1]. Previous studies have shown that the human pancreatic www.impactjournals.com/oncotarget cancer cell line BxPC-3 is dependent on more than one of the HER family members [2, 3]. Pan-HER is highly efficacious against this cancer cell line, and all three target specificities have been shown to contribute to the antiproliferative activity in vivo [1]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
