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Cited by 18Protein Kinase Regulation and GTPase SignalingProtein Tyrosine PhosphatasesMelanoma and MAPK Pathways

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Not just g RAS ping at flaws: Finding vulnerabilities to develop novel therapies for treating KRAS mutant cancers

Open access
Ebi, Hiromichi, Faber, Anthony C., Engelman, Jeffrey A., Yano, Seiji·2014·Cancer Science
DOI 10.1111/cas.12383PMC PMC4317830
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Abstract

Mutations in K irsten rat‐sarcoma ( KRAS ) are well appreciated to be major drivers of human cancers through dysregulation of multiple growth and survival pathways. Similar to many other non‐kinase oncogenes and tumor suppressors, efforts to directly target KRAS pharmaceutically have not yet materialized. As a result, there is broad interest in an alternative approach to develop therapies that induce synthetic lethality in cancers with mutant KRAS , therefore exposing the particular vulnerabilities of these cancers. Fueling these efforts is our increased understanding into the biology driving KRAS mutant cancers, in particular the important pathways that mutant KRAS governs to promote survival. In this mini‐review, we summarize the latest approaches to treat KRAS mutant cancers and the rationale behind them.

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  • Dual MEK/AKT inhibition has failed clinically owing to toxicities caused by direct pathway inhibition in patients.

    “dual MEK/AKT inhibition, while promising in model systems, has failed clinically owing to toxicities caused by direct pathway inhibition in patients (Ebi et al., 2014).”

    From A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution (2017) · cites this paper as Ebi et al., 2014

    In “Targeting PI3K-AKT and MEK-ERK Signaling by Combinatorial Approaches” (page not provided), the review reports promising results in models and says clinical activity appears limited because sufficiently suppressing both pathways without toxicity is difficult. But it also reports partial responses and ongoing trials, so saying dual inhibition has categorically “failed clinically” overstates the source. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Therapies targeting MEK alongside the PI3K/AKT/mTOR pathway have been limited by toxicities, making it difficult to achieve complete pathway inhibition in patients.

    “Therapies targeting MEK alongside the PI3K/AKT/mTOR pathway have been limited by toxicities, making it difficult to achieve complete pathway inhibition in patients”

    From A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution (2017) · cites this paper as Ebi et al., 2014

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Metadata

Authors
Ebi, H., Faber, A. C., Engelman, J. A., & Yano, S.
Affiliations
  • Kanazawa University (JP)
  • Harvard University (US)
Corresponding author
Ebi, Hiromichi
ORCID
Venue
Cancer Science
Publisher
Wiley
Published
2014-03-26
Volume
105
Issue
5
Pages
499-505
ISSN
  • 1347-9032 (ISSN-L)
  • 1349-7006
DOI
10.1111/cas.12383
PMC
PMC4317830
OpenAlex
W2057330346
Cited by
18
References
6
Citations by year
2026: 1 · 2024: 2 · 2022: 2 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 2
FWCI
0.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancer Science (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • Kanazawa University Repository for Academic Resources (DSpace) (Kanazawa University) (submittedVersion, cc-by-nc-nd)
Funders
Japan Society for the Promotion of Science (26830105)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • 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
Keywords
KRAS mutation, KRAS-mutant cancer, synthetic lethality, cancer vulnerability, cancer therapy
MeSH terms
Humans, Mutation, Neoplasms, Proto-Oncogene Proteins, Proto-Oncogene Proteins p21(ras), Apoptosis, Receptor, IGF Type 1, ras Proteins, Proto-Oncogene Proteins c-bcl-2, Phosphatidylinositol 3-Kinases, MAP Kinase Kinase Kinases, MAP Kinase Signaling System, Extracellular Signal-Regulated MAP Kinases, Proto-Oncogene Proteins c-akt, Molecular Targeted Therapy

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