Searching across hundreds of databases
Pharmacologic targeting of components of ERK signaling in ERK-dependent tumors is often limited by adaptive resistance, frequently mediated by feedback-activation of RTK signaling and rebound of ERK activity. Here, we show that combinatorial pharmacologic targeting of ERK signaling and the SHP2 phosphatase prevents adaptive resistance in defined subsets of ERK-dependent tumors. In each tumor that was sensitive to combined treatment, p(Y542)SHP2 induction was observed in response to ERK signaling inhibition. The strategy was broadly effective in TNBC models and tumors with RAS mutations at G12, whereas tumors with RAS(G13D) or RAS(Q61X) mutations were resistant. In addition, we identified a subset of BRAF(V600E) tumors that were resistant to the combined treatment, in which FGFR was found to drive feedback-induced RAS activation, independently of SHP2. Thus, we identify molecular determinants of response to combined ERK signaling and SHP2 inhibition in ERK-dependent tumors.
Pubmed ID: 30605687 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsNon-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsCell line HCC1937 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BT-20 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-468 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line LoVo is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line T-47D is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BT-474 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HT-29 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H358 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCT 15 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BT-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SK-BR-3 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-436 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-157 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-231 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Human KRAS
View all literature mentionsThis polyclonal targets phospho-FGFR-1 (Tyr653/Tyr654)
View all literature mentionsThis monoclonal targets Rat IL-6
View all literature mentionsThis monoclonal targets DUSP6
View all literature mentionsThis monoclonal targets SH-PTP2 (B-1)
View all literature mentionsThis monoclonal targets SHP2 (phospho Y542)
View all literature mentionsThis monoclonal targets basic FGF
View all literature mentionsThis monoclonal targets Met
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis monoclonal targets Met
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis monoclonal targets ERBB3
View all literature mentionsThis monoclonal targets FGF Receptor 1 (D8E4) XP Rabbit mAb
View all literature mentionsThis monoclonal targets EGF Receptor
View all literature mentionsThis monoclonal targets HER3/ErbB3
View all literature mentionsThis monoclonal targets Phospho-Stat3 (Tyr705)
View all literature mentionsThis monoclonal targets MEK1
View all literature mentionsThis monoclonal targets p44 / 42 MAP Kinase
View all literature mentionsThis monoclonal targets Phospho-MEK1/2 (Ser217/221)
View all literature mentionsThis monoclonal targets Phospho-EGF Receptor (Tyr1068)
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204)
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
