Heterogeneity Underlies the Emergence of EGFR T790 Wild-Type Clones Following Treatment of T790M-Positive Cancers with a Third Generation EGFR Inhibitor RUNNING TITLE: T790 Heterogeneity in Rociletinib Resistance
نویسندگان
چکیده
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 Massachusetts General Hospital, Boston, MA Linnea Fulton Massachusetts General Hospital, Boston, MA Aaron N. Hata Massachusetts General Hospital, Boston, MA Elizabeth L. Lockerman Massachusetts General Hospital, Boston, MA Anuj Kalsy Massachusetts General Hospital, Boston, MA Subba Digumarthy Massachusetts General Hospital, Boston, MA Alona Muzikansky Massachusetts General Hospital, Boston, MA Mitch Raponi Clovis Oncology, San Francisco, CA Angel R. Garcia Massachusetts General Hospital, Boston, MA Hillary E. Mulvey Massachusetts General Hospital, Boston, MA Melissa K. Parks Massachusetts General Hospital, Boston, MA Richard H. DiCecca Massachusetts General Hospital, Boston, MA
منابع مشابه
Heterogeneity Underlies the Emergence of EGFRT790 Wild-Type Clones Following Treatment of T790M-Positive Cancers with a Third-Generation EGFR Inhibitor.
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 rociletinib-resistant biopsies. Two T790-wild...
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Rociletinib is a third-generation EGFR inhibitor active in lung cancers with T790M, the gatekeeper mutation underlying most fi rst-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 rociletinib-resistant biopsies. Two T790–wild-type canc...
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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 innearly two thirds of patients.However, acquired resistance mechanisms in patients treated with these drugs are yet to be described. Experimental Desig...
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Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of patients after treatment with first-line in...
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The tyrosine kinase inhibitors (TKI) against epidermal growth factor receptor (EGFR) are widely used in patients with non-small cell lung cancer (NSCLC). However, EGFR T790M mutation leads to resistance to most clinically available EGFR TKIs. Third-generation EGFR TKIs against the T790M mutation have been in active clinical development. These agents include osimertinib, rociletinib, HM61713, AS...
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