Shipping out MEK inhibitor resistance with SHP2 inhibitors
Abstract
Summary: RAS is one of the most frequently altered oncogenes, yet RAS-driven tumors are largely refractory to anticancer therapies. Fedele and colleagues demonstrate that SHP2 inhibitors prevent adaptive MEK inhibitor resistance; therefore, combining MEK and SHP2 inhibitors represents an exciting new therapeutic approach for the treatment of RAS-driven cancers. Cancer Discov; 8(10); 1210–2. ©2018 AACR. See related article by Fedele et al., p. 1237.
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In normal cells, RTKs activate Ras by recruiting the SHC-GRB2-SOS1 complex independent of SHP2.
“In normal cells, RTKs activates Ras by recruiting the SHC-GRB2-SOS1 complex independent of SHP2.85”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [85]
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Atomistic ensemble of active SHP2 phosphatasePreprint
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BindingDB Entry 50022804: Advances in SHP2 tunnel allosteric inhibitors and bifunctional molecules.
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- Authors
- Torres-Ayuso, P., & Brognard, J.
- Affiliations
- Signaling Networks in Cancer Section, Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, Maryland.
- Frederick National Laboratory for Cancer Research (US)
- Venue
- Cancer Discovery
- Published
- 2018-10-01
- Volume
- 8
- Issue
- 10
- Pages
- 1210-1212
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2895494778
- Cited by
- 37
- References
- 10
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 8 · 2023: 5 · 2022: 8 · 2021: 4 · 2020: 8 · 2019: 1
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- SHP2 inhibitors, MEK inhibitors, drug resistance, RAS-driven cancers, oncogenic Ras, combination therapy, MAPK signaling, targeted cancer therapy
- MeSH terms
- Cell Line, Tumor, Protein Kinase Inhibitors
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