The DOI matches its Crossref record; 76 of the 79 references it cites were found in a registry or an index.
A RAS Renaissance: Emerging Targeted Therapies for KRAS-Mutated Non–Small Cell Lung Cancer
Open accessAbstract
Of the numerous oncogenes implicated in human cancer, the most common and perhaps the most elusive to target pharmacologically is RAS. Since the discovery of RAS in the 1960s, numerous studies have elucidated the mechanism of activity, regulation, and intracellular trafficking of the RAS gene products, and of its regulatory pathways. These pathways yielded druggable targets, such as farnesyltransferase, during the 1980s to 1990s. Unfortunately, early clinical trials investigating farnesyltransferase inhibitors yielded disappointing results, and subsequent interest by pharmaceutical companies in targeting RAS waned. However, recent advances including the identification of novel regulatory enzymes (e.g., Rce1, Icmt, Pdeδ), siRNA-based synthetic lethality screens, and fragment-based small-molecule screens, have resulted in a “Ras renaissance,” signified by new Ras and Ras pathway–targeted therapies that have led to new clinical trials of patients with Ras-driven cancers. This review gives an overview of KRas signaling pathways with an emphasis on novel targets and targeted therapies, using non–small cell lung cancer as a case example. Clin Cancer Res; 20(15); 3921–30. ©2014 AACR.
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“KRAS proteins primarily bind to guanosine diphosphate (GDP) and are in an inactive conformation maintained by intrinsic guanosine triphosphate (GTP) hydrolytic activity.”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [6]
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“In addition, a selective non-covalent inhibitor of KRAS (G12D), MRTX1133, also provides a novel targeting therapy [6, 22, 25].”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [6]
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Vinorelbine plus Cisplatin vs. Observation in Resected Non–Small-Cell Lung Cancer
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Targeting KRAS mutant cancers: from druggable therapy to drug resistance
Zhu, C., Guan, X., Zhang, X., Luan, X., Song, Z., Cheng, X., Zhang, W., & Qin, J.-J. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01629-2 · Cited by 231
Unique Genetic and Survival Characteristics of Invasive Mucinous Adenocarcinoma of the Lung
Shim, H. S., Kenudson, M. M., Zheng, Z., Liebers, M. R., Cha, Y. J., Ho, Q. V., Onozato, M. L., Le, L. P., Heist, R. S., & Iafrate, A. J. (2015) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000579 · Cited by 203
KRAS-mutant non-small cell lung cancer: Converging small molecules and immune checkpoint inhibition
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Metadata
- Authors
- Vasan, N., Boyer, J. L., & Herbst, R. S.
- Affiliations
- Massachusetts General Hospital (US)
- Cornell University (US)
- Yale Cancer Center (US)
- Corresponding author
- Herbst, Roy S.
- Venue
- Clinical Cancer Research
- Published
- 2014-07-31
- Volume
- 20
- Issue
- 15
- Pages
- 3921-3930
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC5369356
- OpenAlex
- W1982288880
- Cited by
- 102
- References
- 79
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 5 · 2023: 3 · 2022: 8 · 2021: 6 · 2020: 7 · 2019: 9 · 2018: 10 · 2017: 14 · 2016: 13 · 2015: 14 · 2014: 2
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA155196)
- National Institute of General Medical Sciences (T32GM007205)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- KRAS mutation, non-small cell lung cancer, oncogenic Ras, targeted therapy, Ras signaling, farnesyltransferase inhibitors, RCE1, IcmT, PDEδ, synthetic lethality, siRNA screen, RAS-driven cancers
- MeSH terms
- Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Mutation, Prognosis, Proto-Oncogene Proteins, Signal Transduction, Proto-Oncogene Proteins p21(ras), ras Proteins, Molecular Targeted Therapy
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