Hillary E. Mulvey

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UNLABELLED Rociletinib is a third-generation EGFR inhibitor active in lung cancers with T790M, the gatekeeper mutation underlying most first-generation EGFR drug resistance. We biopsied patients at rociletinib progression to explore resistance mechanisms. Among 12 patients with T790M-positive cancers at rociletinib initiation, six had T790-wild-type(More)
Although mechanisms of acquired resistance of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here we observe that acquired resistance caused by the EGFR(T790M) gatekeeper mutation can occur either by selection of(More)
PURPOSE A secondary EGFR mutation, T790M, is the most common resistance mechanism in EGFR-mutant adenocarcinomas that have progressed on erlotinib. Third-generation EGFR inhibitors capable of inhibiting mutant EGFR with T790M produce responses in nearly two thirds of patients. However, acquired resistance mechanisms in patients treated with these drugs are(More)
Tyrosine kinase inhibitors are effective treatments for non-small-cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) mutations. However, relapse typically occurs after an average of 1 year of continuous treatment. A fundamental histological transformation from NSCLC to small-cell lung cancer (SCLC) is observed in a subset of the(More)
Zofia Piotrowska Massachusetts General Hospital, Boston, MA Matthew J. Niederst Massachusetts General Hospital, Boston, MA Chris A. Karlovich Clovis Oncology, San Francisco, CA Heather A. Wakelee Stanford Cancer Institute, Stanford University, Stanford, CA Joel W. Neal Stanford Cancer Institute, Stanford University, Stanford, CA Mari Mino-Kenudson(More)
Purpose: A secondary EGFR mutation, T790M, is the most common resistance mechanism in EGFR-mutant adenocarcino-mas that have progressed on erlotinib. Third-generation EGFR inhibitors capable of inhibiting mutant EGFR with T790M produce responses in nearly two thirds of patients. However, acquired resistance mechanisms in patients treated with these drugs(More)
Extracellular vesicles (EVs) are secreted from many cells, carrying cargoes including proteins and nucleic acids. Research has shown that EVs play a role in a variety of biological processes including immunity, bone formation and recently they have been implicated in promotion of a metastatic phenotype. EVs were isolated from HCT116 colon cancer cells, 1459(More)
Running Title C797S promotes resistance to third generation EGFR inhibitors Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Acquired resistance to first generation EGFR inhibitors is mediated by a secondary mutation to EGFR, T790M, in just over half of EGFR mutant NSCLC patients. Third generation EGFR(More)
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