Journal ArticleDOI
ERBB receptors and cancer: the complexity of targeted inhibitors.
Nancy E. Hynes,Heidi Lane +1 more
TLDR
This work discusses the significance of these receptors as clinical targets, in particular the molecular mechanisms underlying response, and many ERBB inhibitors used in the clinic.Abstract:
ERBB receptor tyrosine kinases have important roles in human cancer. In particular, the expression or activation of epidermal growth factor receptor and ERBB2 are altered in many epithelial tumours, and clinical studies indicate that they have important roles in tumour aetiology and progression. Accordingly, these receptors have been intensely studied to understand their importance in cancer biology and as therapeutic targets, and many ERBB inhibitors are now used in the clinic. We will discuss the significance of these receptors as clinical targets, in particular the molecular mechanisms underlying response.read more
Citations
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A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer.
Andrea Bertotti,Giorgia Migliardi,Francesco Galimi,Francesco Sassi,Davide Torti,Claudio Isella,Davide Corà,Federica Di Nicolantonio,Michela Buscarino,Consalvo Petti,Dario Ribero,Nadia Russolillo,Andrea Muratore,Paolo Massucco,Alberto Pisacane,Luca Molinaro,Emanuele Valtorta,Andrea Sartore-Bianchi,Mauro Risio,Lorenzo Capussotti,Marcello Gambacorta,Salvatore Siena,Enzo Medico,Anna Sapino,Silvia Marsoni,Paolo M. Comoglio,Alberto Bardelli,Livio Trusolino +27 more
TL;DR: Ciardiello et al. as discussed by the authors found that HER2 amplification was a predictor of resistance to anti-epidermal growth factor receptor (EGFR) antibodies and response to combination therapies against HER2 in this tumor setting.
Journal ArticleDOI
Ligand-Independent HER2/HER3/PI3K Complex Is Disrupted by Trastuzumab and Is Effectively Inhibited by the PI3K Inhibitor GDC-0941
Teemu T. Junttila,Robert W. Akita,Kathryn Parsons,Carter Fields,Gail Lewis Phillips,Lori Friedman,Deepak Sampath,Mark X. Sliwkowski +7 more
TL;DR: A mechanism of action for trastuzumab whereby antibody treatment disrupts ligand-independent HER2/HER3 interactions in HER2-amplified cells is described, leading to downregulation of proximal and distal AKT signaling, and correlates with the antiproliferative effects of trastzumab.
Journal ArticleDOI
Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer
Helena Linardou,Issa J Dahabreh,Dimitra Kanaloupiti,Fotios Siannis,Dimitrios Bafaloukos,Paris Kosmidis,Christos Papadimitriou,Samuel S. Murray +7 more
TL;DR: This analysis provides empirical evidence that k-RAS mutations are highly specific negative predictors of response (de-novo resistance) to single-agent EGFR TKIs in advanced NSCLC; and similarly to anti-EGFR monoclonal antibodies alone or in combination with chemotherapy in patients with mCRC.
Journal ArticleDOI
The Epidermal Growth Factor Receptor Pathway: A Model for Targeted Therapy
Maurizio Scaltriti,José Baselga +1 more
TL;DR: Recent advances in understanding in the mechanisms of receptor activation and function, discovery of primary and secondary EGFR somatic mutations, as well as a new generation of anti-EGFR agents provide new leads on the clinical targeting of this receptor.
Journal ArticleDOI
Activating HER2 Mutations in HER2 Gene Amplification Negative Breast Cancer
Ron Bose,Shyam M. Kavuri,Adam C. Searleman,Wei Shen,Dong Shen,Daniel C. Koboldt,John Monsey,Nicholas Goel,Adam B. Aronson,Shunqiang Li,Cynthia X. Ma,Li Ding,Elaine R. Mardis,Matthew J. Ellis +13 more
TL;DR: It is shown that the majority of HER2 somatic mutations in breast cancer patients are activating mutations that likely drive tumorigenesis and the results suggest that patients with HER2 mutation–positive breast cancers could benefit from existing HER2-targeted drugs.
References
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Journal ArticleDOI
The hallmarks of cancer.
TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
Journal ArticleDOI
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene
Dennis J. Slamon,Gary M. Clark,Steven G. Wong,Wendy J. Levin,Axel Ullrich,William L. McGuire +5 more
TL;DR: Amplification of the HER-2/neu gene was a significant predictor of both overall survival and time to relapse in patients with breast cancer, and had greater prognostic value than most currently used prognostic factors in lymph node-positive disease.
Journal ArticleDOI
Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib
Thomas J. Lynch,Daphne W. Bell,Raffaella Sordella,Sarada Gurubhagavatula,Ross A. Okimoto,Brian W. Brannigan,Patricia L. Harris,Sara M. Haserlat,Jeffrey G. Supko,Frank G. Haluska,David N. Louis,David C. Christiani,Jeff Settleman,Daniel A. Haber +13 more
TL;DR: A subgroup of patients with non-small-cell lung cancer have specific mutations in the EGFR gene which correlate with clinical responsiveness to the tyrosine kinase inhibitor gefitinib, and these mutations lead to increased growth factor signaling and confer susceptibility to the inhibitor.
Journal ArticleDOI
Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2
Dennis J. Slamon,Brian Leyland-Jones,Steven Shak,Hank Fuchs,Virginia E. Paton,Alex Bajamonde,Thomas Fleming,Wolfgang Eiermann,Janet M. Wolter,Mark D. Pegram,José Baselga,Larry Norton +11 more
TL;DR: The addition of trastuzumab to chemotherapy was associated with a longer time to disease progression, a higher rate of objective response, a longer duration of response, and a lower rate of death at 1 year.
Journal ArticleDOI
EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.
J. Guillermo Paez,Pasi A. Jänne,Pasi A. Jänne,Jeffrey C. Lee,Sean Tracy,Heidi Greulich,Heidi Greulich,Stacey Gabriel,Paula Herman,Frederic J. Kaye,Neal I. Lindeman,Titus J. Boggon,Katsuhiko Naoki,Hidefumini Sasaki,Yoshitaka Fujii,Michael J. Eck,William R. Sellers,William R. Sellers,William R. Sellers,Bruce E. Johnson,Bruce E. Johnson,Matthew Meyerson,Matthew Meyerson +22 more
TL;DR: Results suggest that EGFR mutations may predict sensitivity to gefitinib, and treatment with the EGFR kinase inhibitor gefitsinib causes tumor regression in some patients with NSCLC, more frequently in Japan.
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