KRAS as a Therapeutic Target

McCormick, Frank

doi:10.1158/1078-0432.ccr-14-2662

Cited by 321Protein Kinase Regulation and GTPase SignalingMelanoma and MAPK PathwaysProtein Tyrosine Phosphatases

KRAS as a Therapeutic Target

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McCormick, Frank·2015·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-14-2662PMC PMC4407814

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Abstract

KRAS proteins play a major role in human cancer, but have not yielded to therapeutic attack. New technologies in drug discovery and insights into signaling pathways that KRAS controls have promoted renewed efforts to develop therapies through direct targeting of KRAS itself, new ways of blocking KRAS processing, or by identifying targets that KRAS cancers depend on for survival. Although drugs that block the well-established downstream pathways, RAF–MAPK and PI3K, are being tested in the clinic, new efforts are under way to exploit previously unrecognized vulnerabilities, such as altered metabolic networks, or novel pathways identified through synthetic lethal screens. Furthermore, new ways of suppressing KRAS gene expression and of harnessing the immune system offer further hope that new ways of treating KRAS are finally coming into view. These issues are discussed in this edition of CCR Focus. Clin Cancer Res; 21(8); 1797–801. ©2015 AACR. See all articles in this CCR Focus section, “Targeting RAS-Driven Cancers.”

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KRAS is the most dominant mutated subtype in the RAS family and is responsible for 85% of RAS gene-driven cancers, particularly in pancreatic, colorectal, and lung cancers.
“It is the most dominant mutated subtype in the RAS family and is responsible for 85% of RAS gene-driven cancers, particularly in pancreatic, colorectal, and lung cancers.40–42”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [40]
Oncogenic KRAS can activate various downstream effector pathways, and the best characterized are PI3K and MAPK.
“Oncogenic KRAS can activate various downstream effector pathways, and the best characterized are phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinases (MAPK) (23–25).”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [23]

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Authors: McCormick, F.
Affiliations: Frederick National Laboratory for Cancer Research (US)
Corresponding author: McCormick, Frank
ORCID: McCormick, Frank
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2015-04-14
Volume: 21
Issue: 8
Pages: 1797-1801
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-14-2662
PMC: PMC4407814
OpenAlex: W2062410054
Cited by: 320
References: 41
Citations by year: 2026: 10 · 2025: 22 · 2024: 18 · 2023: 35 · 2022: 26 · 2021: 32 · 2020: 45 · 2019: 35 · 2018: 31 · 2017: 29 · 2016: 26 · 2015: 10
FWCI: 3.10
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Cancer Institute (U01CA168370)
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 › Melanoma and MAPK Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords: KRAS, KRAS-targeted therapy, MAPK/ERK pathway, PI3K signaling, synthetic lethality, cancer metabolism, cancer immunotherapy, KRAS oncogenic signaling, drug discovery
MeSH terms: Animals, Antineoplastic Agents, Cell Transformation, Neoplastic, Humans, Immunity, Immunotherapy, Mutation, Neoplasms, Genetic Therapy, Signal Transduction, Proto-Oncogene Proteins p21(ras), Drug Resistance, Neoplasm, Protein Subunits, RNA Interference, RNA, Small Interfering, Protein Kinase Inhibitors, Molecular Targeted Therapy

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