Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors

Science Translational Medicine

Volumn 3, Issue 75, 2011, Pages

  Sequist, Lecia V ^a,b   Waltman, Belinda A ^b   Dias Santagata, Dora ^b,c   Digumarthy, Subba ^b,c   Turke, Alexa B ^a,b   Fidias, Panos ^a,b   Bergethon, Kristin ^c   Shaw, Alice T ^a,b   Gettinger, Scott ^d   Cosper, Arjola K ^a   Akhavanfard, Sara ^b,c   Heist, Rebecca S ^a,b   Temel, Jennifer ^a,b   Christensen, James G ^e   Wain, John C ^a,b,c   Lynch, Thomas J ^d   Vernovsky, Kathy ^a   Mark, Eugene J ^b,c   Lanuti, Michael ^a,b,c   Iafrate, A John ^b,c   Mino Kenudson, Mari ^b,c   Engelman, Jeffrey A ^a,b   more..

^a MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

^d YALE CANCER CENTER   (United States)

^e PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

APC PROTEIN; B RAF KINASE; BETA CATENIN; EPIDERMAL GROWTH FACTOR RECEPTOR; ERLOTINIB; GEFITINIB; K RAS PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN P53; SCATTER FACTOR RECEPTOR; ANTINEOPLASTIC AGENT; PROTEIN KINASE INHIBITOR; QUINAZOLINE DERIVATIVE;

ADENOSQUAMOUS CARCINOMA; ADULT; AGED; ARTICLE; CANCER CHEMOTHERAPY; CANCER MORPHOLOGY; CANCER PATIENT; CANCER RESISTANCE; CELL GROWTH; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG RECEPTOR BINDING; DRUG RESPONSE; DRUG SENSITIVITY; EPITHELIAL MESENCHYMAL TRANSITION; FEMALE; GENE; GENE AMPLIFICATION; GENE MUTATION; GENOTYPE; HUMAN; HUMAN TISSUE; LUNG ADENOCARCINOMA; LUNG NON SMALL CELL CANCER; LUNG PARENCHYMA; LUNG SMALL CELL CANCER; MALE; MUTATIONAL ANALYSIS; PHOSPHATIDYLINOSITOL 3 KINASE GENE; PRIORITY JOURNAL; PROTEIN FUNCTION; TUMOR BIOPSY; BIOPSY; DRUG ANTAGONISM; DRUG RESISTANCE; GENETICS; LUNG TUMOR; MIDDLE AGED; MUTATION; PATHOLOGY; PHENOTYPE;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; BIOPSY; DRUG RESISTANCE, NEOPLASM; FEMALE; GENOTYPE; HUMANS; LUNG NEOPLASMS; MALE; MIDDLE AGED; MUTATION; PHENOTYPE; PROTEIN KINASE INHIBITORS; QUINAZOLINES; RECEPTOR, EPIDERMAL GROWTH FACTOR;

EID: 79953118839     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3002003     Document Type: Article

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65. Acknowledgments: We thank A. Muzikansky and E. Bast for their help with data analysis. Funding: This study is supported by grants from Uniting Against Lung Cancer, sponsored by UALC: New England and the Marjorie E. Korff Fund (L.V.S.), the NIH Gastrointestinal Cancer SPORE P50 CA127003 (J.A.E. and M.M.-K.), K08 grant CA120060-01 (J.A.E.), R01CA137008-01 (J.A.E.), R01CA140594 (J.A.E.), 1U01CA141457-01 (J.A.E.), National Cancer Institute Lung SPORE P50CA090578 (J.A.E.), Dana-Farber/Harvard Cancer Center, the American Association for Cancer Research (J.A.E.), the V Foundation (J.A.E.), American Cancer Society RSG-06-102-01-CCE (J.A.E.), the Ellison Foundation Scholar (J.A.E.), and the Doris Duke Charitable Foundation (B.A.W.). This work was supported by a gift from the Daniel Crane Foundation. Author contributions: L.V.S., B.A.W., D.D.-S., A.J.I., M.M.-K., and J.A.E. were responsible for the concept and design of the study. L.V.S., P.F., A.T.S., S.G., R.S.H., J.T., J.C.W., T.J.L., M.L., and J.A.E. were responsible for identifying and providing patients. S.D., J.C.W., and M.L. were responsible for performing patient biopsies. D.D.-S., A.B.T., K.B., A.K.C., S.A., K.V., E.J.M., A.J.I., M.M.-K., and J.A.E. were responsible for laboratory analyses. S.D. was responsible for radiographic analyses. J.G.C. provided the PF00299804 compound. L.V.S., B.A.W., D.D.-S., M.M.-K., and J.A.E. were primarily responsible for writing the manuscript. All authors contributed to manuscript editing and approval. Competing interests: P.F. is an advisor to Genentech. D.D.-S. has a paid consulting relationship with Bio-Reference Laboratories Inc. D.D.-S. and A.J.I. are inventors on a patent filed for SNaPshot genotyping methods (U.S. patent number 12/799415). J.A.E. holds equity in Gatekeeper and is a co-inventor on a patent pertaining to the use of combined MET and EGFR inhibitors (U.S. patent number 12/450826). T.J.L. is an advisor to Boehringer-Ingelheim, Supergen, Merck, AstraZeneca, and Genentech; is on the Board of Directors of Infinity Pharmaceuticals; and is also an inventor on a patent held by Partners Healthcare for EGFR mutation testing (U.S. patent numbers 11/894135, 11/894159, and 11/894160). Other authors declare no competing interests.