“Pathway drug cocktail”: targeting Ras signaling based on structural pathways
Open accessAbstract
Tumors bearing Ras mutations are notoriously difficult to treat. Drug combinations targeting the Ras protein or its pathway have also not met with success. 'Pathway drug cocktails', which are combinations aiming at parallel pathways, appear more promising; however, to be usefully exploited, a repertoire of classified pathway combinations is desirable. This challenge would be facilitated by the availability of the structural network of signaling pathways. When integrated with functional and systems level clinical data, they can be powerful in advancing novel therapeutic platforms. Based on structural knowledge, drug cocktails may tear into multiple cellular processes that drive tumorigenesis, and help in deciphering the interrelationship between Ras mutations and the rewired Ras network. The pathway drug cocktail paradigm can be applied to other signaling protein targets.
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K-Ras protein has a relatively smooth surface with few well-characterized hydrophobic pockets where compounds could bind.
“First, K-Ras protein has a relatively smooth surface, with few well-characterized hydrophobic pockets where compounds could bind.41,44”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [44]
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References 72 · Cited by 62
- Authors
- Nussinov, R., Tsai, C.-J., & Mattos, C.
- Affiliations
- Tel Aviv University (IL)
- National Cancer Institute (US)
- Northeastern University (US)
- Corresponding author
- Nussinov, Ruth
- Venue
- Trends in Molecular Medicine
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 19
- Issue
- 11
- Pages
- 695-704
- ISSN
- 1471-4914 (ISSN-L)
- OpenAlex
- W2058481347
- Cited by
- 62
- References
- 72
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2021: 3 · 2020: 5 · 2019: 6 · 2018: 4 · 2017: 7 · 2016: 8 · 2015: 14 · 2014: 7 · 2013: 2
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- green
- arxiv.org
- Locations
- Trends in Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion)
- arXiv (Cornell University)
- Funders
- National Institutes of Health
- U.S. Public Health Service (HHSN261200800001E)
- National Cancer Institute (R56CA096867)
- 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 › Bioinformatics and Genomic Networks
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- Ras signaling, drug combination therapy, RAS mutations, cancer therapy, carcinogenesis
- MeSH terms
- Animals, Antineoplastic Combined Chemotherapy Protocols, Drug Therapy, Combination, Humans, Neoplasms, Signal Transduction, ras Proteins
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