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Paula J. Spitzler
Researcher at Vanderbilt University
Publications - 4
Citations - 2442
Paula J. Spitzler is an academic researcher from Vanderbilt University. The author has contributed to research in topics: T790M & Rociletinib. The author has an hindex of 4, co-authored 4 publications receiving 2053 citations.
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Journal ArticleDOI
AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer
Darren Cross,Susan Ashton,Serban Ghiorghiu,Cath Eberlein,Caroline A. Nebhan,Paula J. Spitzler,Jonathon P. Orme,M. Raymond V. Finlay,Richard A. Ward,Martine J. Mellor,Gareth D Hughes,Amar Rahi,Vivien Jacobs,Monica Red Brewer,Eiki Ichihara,Jing Sun,Hailing Jin,Peter Ballard,Katherine Al-Kadhimi,Rachel Rowlinson,Teresa Klinowska,Graham Richmond,Mireille Cantarini,Dong Wan Kim,Malcolm R Ranson,William Pao +25 more
TL;DR: A novel structurally distinct third-generation EGFR TKI that irreversibly and selectively targets both sensitizing and resistant T790M(+) mutant EGFR while harboring less activity toward wild-type EGFR is reported.
Journal ArticleDOI
HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutation.
Ken Takezawa,Valentina Pirazzoli,Maria E. Arcila,Caroline A. Nebhan,Xiaoling Song,Elisa de Stanchina,Kadoaki Ohashi,Yelena Y. Janjigian,Paula J. Spitzler,Mary Ann Melnick,G. J. Riely,Mark G. Kris,Vincent A. Miller,Marc Ladanyi,Katerina Politi,William Pao +15 more
TL;DR: It is shown in vitro and in vivo that afatinib plus cetuximab significantly inhibits HER2 phosphorylation, and this results reveal a previously unrecognized mechanism of resistance to EGFR-TKIs and provide a rationale to assess the status and possibly target HER2 in EG FR-mutant tumors with acquired resistance toEGFR- TKIs.
Journal ArticleDOI
Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models
Catherine Anne Eberlein,Daniel Stetson,Aleksandra Markovets,Katherine Al-Kadhimi,Zhongwu Lai,Paul R. Fisher,Catherine B. Meador,Paula J. Spitzler,Eiki Ichihara,Sarah Ross,Miika Ahdesmaki,Ambar Ahmed,Laura E. Ratcliffe,Elizabeth L. Christey O'Brien,Claire Barnes,Henry Brown,Paul D. Smith,Jonathan R. Dry,Garry Beran,Kenneth S. Thress,Brian Dougherty,William Pao,Darren Cross +22 more
TL;DR: The detection of heterogeneous mechanisms of resistance within populations of EGFR-mutant cells with acquired resistance to current and newly developed EGFR tyrosine kinase inhibitors, including AZD9291, and NRAS modifications in tumor samples from patients who have progressed on current or EGFR inhibitors in development are described.
Proceedings ArticleDOI
Abstract A109: AZD9291: an irreversible, potent and selective third generation tyrosine kinase inhibitor (TKI) targeting EGFR activating (EGFRm+) and resistance (T790M) mutations in advanced lung adenocarcinoma.
Darren Cross,Sue Ashton,Caroline A. Nebhan,Cath Eberlein,M. Raymond V. Finlay,Gareth Hughes,Vivien Jacobs,Martine J. Mellor,Monica Red Brewer,Catherine B. Meador,Jonathon P. Orme,Paula J. Spitzler,Steve Powell,Amar Rahi,Paula Taylor,Richard A. Ward,Paula Daunt,Anne Galer,Teresa Klinowska,Graham Richmond,William Pao +20 more
TL;DR: Preclinical data demonstrates that AZD9291 is a potent and effective inhibitor of both EGFR activating ( EGFRm+) and resistance (EGFRm+/T790M) mutations whilst sparing wild-type EGFR, and indicates that it could target tumours that have acquired resistance to the more recently identified HER2-amplification mechanism, thus potentially extending its benefit in TKI resistant patients.