The DOI matches its Crossref record; 212 of the 212 references it cites were found in a registry or an index.
Anticancer drug resistance: An update and perspective
Open accessAbstract
inhibitors are variable and fall into three categories, (i) new point mutations in KRas, or multiple copies of KRAS G12C which lead to higher expression level of the mutant protein; (ii) mutations in genes other than KRAS; (iii) original cancer transitioning to other cancer(s). Resistance to adagrasib, an experimental antitumor agent exerting its cytotoxic effect as a covalent inhibitor of the G12C KRas, indicated that half of the cases present multiple KRas mutations as well as allele amplification. Redundant or parallel pathways included MET amplification; emerging driver mutations in NRAS, BRAF, MAP2K1, and RET; gene fusion events in ALK, RET, BRAF, RAF1, and FGFR3; and loss-of-function mutations in NF1 and PTEN tumor suppressors. In the current review we discuss the molecular mechanisms underlying drug resistance while focusing on those emerging to common targeted cancer drivers. We also address questions of why cancers with a common driver mutation are unlikely to evolve a common drug resistance mechanism, and whether one can predict the likely mechanisms that the tumor cell may develop. These vastly important and tantalizing questions in drug discovery, and broadly in precision medicine, are the focus of our present review. We end with our perspective, which calls for target combinations to be selected and prioritized with the help of the emerging massive compute power which enables artificial intelligence, and the increased gathering of data to overcome its insatiable needs.
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1 retracted
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MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
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Cited by
Unveiling the mechanisms and challenges of cancer drug resistance
Khan, S. U., Fatima, K., Aisha, S., & Malik, F. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-023-01302-1 · Cited by 417
Allostery: Allosteric Cancer Drivers and Innovative Allosteric Drugs
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Self-citationLiu, Y., Zhang, W., Jang, H., & Nussinov, R. (2025) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.4c02022 · Cited by 10
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Metadata
- Authors
- Nussinov, R., Tsai, C.-J., & Jang, H.
- Venue
- Drug Resistance Updates
- Publisher
- Elsevier BV
- Published
- 2021-12
- Volume
- 59
- Pages
- 100796
- ISSN
- 1368-7646 (ISSN-L)
- OpenAlex
- W4200191138
- Cited by
- 386
- References
- 212
- FWCI
- 32.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
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