ErbB receptors: from oncogenes to targeted cancer therapies
Hongtao Zhang,Alan Berezov,Qiang Wang,Geng Zhang,Jeffrey A. Drebin,Ramachandran Murali,Mark I. Greene +6 more
Reads0
Chats0
TLDR
Current therapy has not yet been optimized, allowing for opportunities for optimization of the next generation of targeted therapy, particularly with regards to inhibiting heteromeric ErbB family receptor complexes.Abstract:
Understanding the genetic origin of cancer at the molecular level has facilitated the development of novel targeted therapies. Aberrant activation of the ErbB family of receptors is implicated in many human cancers and is already the target of several anticancer therapeutics. The use of mAbs specific for the extracellular domain of ErbB receptors was the first implementation of rational targeted therapy. The cytoplasmic tyrosine kinase domain is also a preferred target for small compounds that inhibit the kinase activity of these receptors. However, current therapy has not yet been optimized, allowing for opportunities for optimization of the next generation of targeted therapy, particularly with regards to inhibiting heteromeric ErbB family receptor complexes.read more
Citations
More filters
Journal Article
Novel mechanisms of glucocorticoid resistance in childhood acute lymphoblastic leukemia.
TL;DR: It is reported that PTEN activation contributes to trastuzumab's antitumor activity and PTEN deficiency is a powerful predictor for trastzumab resistance, suggesting that PI3K-targeting therapies could overcome this resistance.
Journal ArticleDOI
Targeting cellular metabolism to improve cancer therapeutics
TL;DR: The relationship between dysregulated cellular metabolism and cancer drug resistance is discussed and how targeting of metabolic enzymes can enhance the efficacy of common therapeutic agents or overcome resistance to chemotherapy or radiotherapy is discussed.
Journal ArticleDOI
Target Binding Properties and Cellular Activity of Afatinib (BIBW 2992), an Irreversible ErbB Family Blocker.
Flavio Solca,Göran Dahl,Andreas Zoephel,Gerd Bader,Michael P. Sanderson,Christian Klein,Oliver Kraemer,Frank Himmelsbach,Eric E. J. Haaksma,Guenther Adolf +9 more
TL;DR: The results stress the importance of the acrylamide group and show that afatinib differs from approved ErbB targeting agents by irreversibly inhibiting the kinase activity of all ErBB family members.
Journal ArticleDOI
SERS Nanoparticles in Medicine: From Label-Free Detection to Spectroscopic Tagging.
TL;DR: Spectroscopic Tagging helps clarify the role of X-ray diffraction in the determination of Higgs boson levels in the response of EMTs to injury.
Journal ArticleDOI
Overall Survival Benefit With Lapatinib in Combination With Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Final Results From the EGF104900 Study
Kimberly L. Blackwell,Harold J. Burstein,Anna Maria Storniolo,Hope S. Rugo,George W. Sledge,Gursel Aktan,Catherine E. Ellis,A. Florance,Svetislava J. Vukelja,Joachim Bischoff,José Baselga,Joyce O'Shaughnessy +11 more
TL;DR: These data demonstrated a significant 4.5-month median OS advantage with the lapatinib and trastuzumab combination and support dual HER2 blockade in patients with heavily pretreated HER2-positive MBC.
References
More filters
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.
Journal ArticleDOI
Untangling the ErbB signalling network
Yosef Yarden,Mark X. Sliwkowski +1 more
TL;DR: When epidermal growth factor and its relatives bind the ErbB family of receptors, they trigger a rich network of signalling pathways, culminating in responses ranging from cell division to death, motility to adhesion.