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
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Cancer stem cells and their mechanism of chemo-radiation resistance.
TL;DR: Signaling pathways involved in the regulation of proliferation and differentiation of stem cells and efficient ABC transporter systems and DNA damage response machineries are starting to be identified as the means by which CSCs out-survive their non-CSC neighbors after conventional anti-cancer treatments.
Journal ArticleDOI
ERBB2 influences the subcellular localization of the estrogen receptor in tamoxifen-resistant MCF-7 cells leading to the activation of AKT and RPS6KA2
Sunil Pancholi,Anne E. Lykkesfeldt,Caroline Hilmi,Susana Banerjee,Alexandra Leary,Suzanne Drury,Stephen S. Johnston,Mitch Dowsett,Lesley-Ann Martin +8 more
TL;DR: It is demonstrated that tamoxifen-resistant cells have the ability to switch between ERBB2 or ESR1 pathways promoting cell growth and that pharmacological inhibition of ER BB2 may be a therapeutic strategy for overcoming tamoxIFen resistance.
Journal ArticleDOI
Targeting EGFR-PI3K-AKT-mTOR signaling enhances radiosensitivity in head and neck squamous cell carcinoma
TL;DR: The frequent activation of the EGFR-PI3K-AKT-mTOR pathway in HNSCC and its implication in the context of radiosensitivity make this pathway one of the most promising targets in the therapy of H NSCC patients.
Journal ArticleDOI
New findings on primary and acquired resistance to anti-EGFR therapy in metastatic colorectal cancer: do all roads lead to RAS?
Giuseppe Bronte,Nicola Silvestris,Marta Castiglia,Antonio Galvano,Francesco Passiglia,Giovanni Sortino,Giuseppe Cicero,Christian Rolfo,Marc Peeters,Viviana Bazan,Daniele Fanale,Antonio Giordano,Antonio Giordano,Antonio Russo +13 more
TL;DR: Liquid biopsy, which helps to isolate circulating tumor DNA, is an innovative method to study both primary and acquired resistance to anti-EGFR monoclonal antibodies, however, high-sensitivity techniques should be used to enable the identification of a wide set of gene mutations related to resistance.
Journal ArticleDOI
Phase I study of continuous afatinib (BIBW 2992) in patients with advanced non-small cell lung cancer after prior chemotherapy/erlotinib/gefitinib (LUX-Lung 4).
Haruyasu Murakami,Tomohide Tamura,Toshiaki Takahashi,Hiroshi Nokihara,Tateaki Naito,Yukiko Nakamura,Kazuto Nishio,Yoko Seki,Akiko Sarashina,Mehdi Shahidi,Noboru Yamamoto +10 more
TL;DR: This Phase I study determined the maximum-tolerated dose (MTD) of afatinib, an irreversible inhibitor of epidermal growth factor receptor (EGFR)1 and 2, up to a dose of 50 mg/day in advanced non-small cell lung cancer (NSCLC), to establish the recommended dose for Phase II.
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
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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.
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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
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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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