@article{5e22b7619166477d99e4736a2f78afc2,
title = "Epidermal Growth Factor Receptor Extracellular Domain Mutations in Glioblastoma Present Opportunities for Clinical Imaging and Therapeutic Development",
abstract = "We explored the clinical and pathological impact of epidermal growth factor receptor (EGFR) extracellular domain missense mutations. Retrospective assessment of 260 de novo glioblastoma patients revealed a significant reduction in overall survival of patients having tumors with EGFR mutations at alanine 289 (EGFRA289D/T/V). Quantitative multi-parametric magnetic resonance imaging analyses indicated increased tumor invasion for EGFRA289D/T/V mutants, corroborated in mice bearing intracranial tumors expressing EGFRA289V and dependent on ERK-mediated expression of matrix metalloproteinase-1. EGFRA289V tumor growth was attenuated with an antibody against a cryptic epitope, based on in silico simulation. The findings of this study indicate a highly invasive phenotype associated with the EGFRA289V mutation in glioblastoma, postulating EGFRA289V as a molecular marker for responsiveness to therapy with EGFR-targeting antibodies.",
keywords = "A289D/T/V, EGFR, EGFR oncogenes, EGFR targeted therapy, GBM, glioblastoma, glioma, radiogenomics, radiomics, survival",
author = "Binder, {Zev A.} and Thorne, {Amy Haseley} and Spyridon Bakas and Wileyto, {E. Paul} and Michel Bilello and Hamed Akbari and Saima Rathore and Ha, {Sung Min} and Logan Zhang and Ferguson, {Cole J.} and Sonika Dahiya and Bi, {Wenya Linda} and Reardon, {David A.} and Ahmed Idbaih and Joerg Felsberg and Bettina Hentschel and Michael Weller and Bagley, {Stephen J.} and Morrissette, {Jennifer J.D.} and Nasrallah, {MacLean P.} and Jianhui Ma and Ciro Zanca and Scott, {Andrew M.} and Laura Orellana and Christos Davatzikos and Furnari, {Frank B.} and O'Rourke, {Donald M.}",
note = "Funding Information: Spyridon Bakas has a patent application related to the detection of EGFRvIII mutation by imaging methods that are different from the ones used herein. David Reardon has received support from Acerta Pharmaceuticals, Agenus, Celldex, EMD Serono, Incyte, Midatech, Omniox, and Tragara. He is a consultant for and has received honoraria from Abbvie, Agenus, Bristol-Myers Squibb, Celldex, EMD Serono, Genentech/Roche, Inovio, Merck, Merck KGaA, Monteris, Novocure, Oncorus, Oxigene, Regeneron, Stemline, Taiho Oncology. Ahmed Idbaih has received support from Carthera, BMS, Hoffmann-La Roche, and Cipla. Michael Weller has received research grants from Abbvie, Acceleron, Actelion, Bayer, Merck, Sharp & Dohme (MSD), Merck (EMD), Novocure, OGD2, Piqur, Roche, and Tragara, and honoraria for lectures or advisory board participation or consulting from Abbvie, BMS, Celgene, Celldex, Merck, Sharp & Dohme (MSD), Merck (EMD), Novocure, Orbus, Pfizer, Progenics, Roche, Teva, and Tocagen. Jennifer Morrissette is a consultant for Novartis. Andrew Scott is an inventor on patents related to mAb806 and has received research support from Abbvie, National Health and Medical Research Council, and Cancer Council Victoria. He is also a consultant with Life Science Pharmaceuticals. Christos Davatzikos has a patent application related to the detection of EGFRvIII mutation by imaging methods that are different from the ones used herein. Frank Furnari is an inventor on patent 9,023,356 on a treatment method using EGFR antibodies and src inhibitors in related formulations. Donald O'Rourke is an inventor on patents 7,625,558 and 6,417,168 held by the University of Pennsylvania on methods of treating cancer cells with erbB inhibition and cytotoxic therapy. In addition, he has a patent application related to the detection of EGFRvIII mutation by imaging methods that are different from the ones used herein. Funding Information: We would like to thank the following organizations for their support: Templeton Family Initiative in Neuro-Oncology (to Z.A.B.); NCI : 2T32CA009523-29A1 (to A.H.T.); Ligue National Contre le Cancer (to A.I.); Lawski Fund for Biomedical Research (to L.O.); NINDS : R01NS042645 (to C.D. and D.M.O.), NCI: U24CA189523 , NCATS : UL1TR001878 , ITMAT of the University of Pennsylvania (to S.B., C.D., and D.M.O.); NBTS: Defeat GBM Research Collaborative , NIH : RO1NS080939 (to F.F). We would also like to thank Kent Osborn, D.V.M., Ph.D., Associate Director for the Animal Care Program at UCSD, and Enrico Radaelli, M.S., V.M.D., D.E.C.V.P., Technical Director for the Comparative Pathology Core in the Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, for their assistance with histology. Funding Information: Spyridon Bakas has a patent application related to the detection of EGFRvIII mutation by imaging methods that are different from the ones used herein. David Reardon has received support from Acerta Pharmaceuticals , Agenus , Celldex , EMD Serono , Incyte , Midatech , Omniox , and Tragara . He is a consultant for and has received honoraria from Abbvie, Agenus, Bristol-Myers Squibb, Celldex, EMD Serono, Genentech/Roche, Inovio, Merck, Merck KGaA, Monteris, Novocure, Oncorus, Oxigene, Regeneron, Stemline, Taiho Oncology. Ahmed Idbaih has received support from Carthera , BMS , Hoffmann-La Roche , and Cipla . Michael Weller has received research grants from Abbvie , Acceleron , Actelion , Bayer , Merck, Sharp & Dohme (MSD), Merck (EMD) , Novocure , OGD2 , Piqur , Roche , and Tragara, and honoraria for lectures or advisory board participation or consulting from Abbvie, BMS, Celgene, Celldex, Merck, Sharp & Dohme (MSD), Merck (EMD), Novocure, Orbus, Pfizer, Progenics, Roche, Teva, and Tocagen. Jennifer Morrissette is a consultant for Novartis. Andrew Scott is an inventor on patents related to mAb806 and has received research support from Abbvie, National Health and Medical Research Council , and Cancer Council Victoria . He is also a consultant with Life Science Pharmaceuticals. Christos Davatzikos has a patent application related to the detection of EGFRvIII mutation by imaging methods that are different from the ones used herein. Frank Furnari is an inventor on patent 9,023,356 on a treatment method using EGFR antibodies and src inhibitors in related formulations. Donald O'Rourke is an inventor on patents 7,625,558 and 6,417,168 held by the University of Pennsylvania on methods of treating cancer cells with erbB inhibition and cytotoxic therapy. In addition, he has a patent application related to the detection of EGFRvIII mutation by imaging methods that are different from the ones used herein. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = jul,
day = "9",
doi = "10.1016/j.ccell.2018.06.006",
language = "English",
volume = "34",
pages = "163--177.e7",
journal = "Cancer Cell",
issn = "1535-6108",
number = "1",
}