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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Targeting the muc1-c oncoprotein downregulates her2 activation and abrogates trastuzumab resistance in breast cancer cells
Deepak Raina,Yasumitsu Uchida,Akriti Kharbanda,Hasan Rajabi,Govind Panchamoorthy,Caining Jin,Surender Kharbanda,Maurizio Scaltriti,José Baselga,Donald Kufe +9 more
TL;DR: The present studies demonstrate that silencing MUC1 C-terminal subunit (MUC1-C) in HER2-overexpressing SKBR3 and BT474 breast cancer cells results in the downregulation of constitutive HER2 activation, indicating that MUC 1-C contributes to constitutive activation of the HER2 pathway and that targeting MUC2-C represents a potential approach to abrogate trastuzumab resistance.
Journal ArticleDOI
Randomized phase Ib/II trial of rilotumumab or ganitumab with panitumumab versus panitumumab alone in patients with wild-type KRAS metastatic colorectal cancer.
Eric Van Cutsem,Cathy Eng,Elżbieta Nowara,Anna Swieboda-Sadlej,Niall C. Tebbutt,Edith P. Mitchell,Irina Davidenko,Joe Stephenson,Elena Elez,Hans Prenen,Hongjie Deng,Rui Tang,Ian McCaffery,Ian McCaffery,Kelly S. Oliner,Lisa Chen,Jennifer Gansert,Elwyn Loh,D. Smethurst,Josep Tabernero +19 more
TL;DR: This is the first study to suggest a benefit for combining an HGF inhibitors with panitumumab in previously treated patients with wild-type KRAS mCRC, and the prespecified criterion for improvement in ORR was met.
Journal ArticleDOI
Role of heregulin in human cancer.
TL;DR: Heregulin is a soluble secreted growth factor, which, upon binding and activation of ErbB3 and Erb B4 transmembrane receptor tyrosine kinases, is involved in cell proliferation, invasion, survival and differentiation of normal and malignant tissues.
Journal ArticleDOI
Development of cellular signaling pathway inhibitors as new antivirals against influenza.
TL;DR: Novel approaches and compounds that target the Raf/MEK/ERK signaling pathway, NF-κB signaling, the PI3K/Akt pathway and the PKC signaling cascade are reviewed, suggesting they offer a new approach to the treatment of influenza, supplementing direct-acting antiviral drugs.
Journal ArticleDOI
Cellular uptake and intracellular trafficking of oligonucleotides: implications for oligonucleotide pharmacology.
TL;DR: In this paper, the authors provide background information on the basic processes of endocytosis and trafficking and then review recent literature on targeted delivery and subcellular trafficking of oligonucleotides in that context.
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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