The DOI matches its Crossref record; 183 of the 188 references it cites were found in a registry or an index.
A view on drug resistance in cancer
Open accessAbstract
The problem of resistance to therapy in cancer is multifaceted. Here we take a reductionist approach to define and separate the key determinants of drug resistance, which include tumour burden and growth kinetics; tumour heterogeneity; physical barriers; the immune system and the microenvironment; undruggable cancer drivers; and the many consequences of applying therapeutic pressures. We propose four general solutions to drug resistance that are based on earlier detection of tumours permitting cancer interception; adaptive monitoring during therapy; the addition of novel drugs and improved pharmacological principles that result in deeper responses; and the identification of cancer cell dependencies by high-throughput synthetic lethality screens, integration of clinico-genomic data and computational modelling. These different approaches could eventually be synthesized for each tumour at any decision point and used to inform the choice of therapy.
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“Mechanistically, low dependency on K-Ras signaling could confer intrinsic resistance to K-RasG12C inhibitors.12,58,61”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [61]
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“In the clinic, intrinsic and acquired resistance may co-exist and intertwine in the same patient treated with K-RasG12C-targeted therapies.57,61”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [61]
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“Complete and durable responses to targeted cancer therapies are rare in patients with advanced-stage cancers.61”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [61]
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NF-κB in biology and targeted therapy: new insights and translational implications
Guo, Q., Jin, Y., Chen, X., Ye, X., Shen, X., Lin, M., Zeng, C., Zhou, T., & Zhang, J. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01757-9 · Cited by 2,405
Mitochondrial dynamics in health and disease: mechanisms and potential targets
Chen, W., Zhao, H., & Li, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01547-9 · Cited by 1,306
Unlocking the potential of antibody–drug conjugates for cancer therapy
Drago, J. Z., Modi, S., & Chandarlapaty, S. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00470-8 · Cited by 1,209
Toward personalized treatment approaches for non-small-cell lung cancer
Wang, M., Herbst, R. S., & Boshoff, C. (2021) · Nature Medicine · doi:10.1038/s41591-021-01450-2 · Cited by 1,127
Metadata
- Authors
- Vasan, N., Baselga, J., & Hyman, D. M.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Hyman, David M.
- Venue
- Nature
- Published
- 2019-11-13
- Volume
- 575
- Issue
- 7782
- Pages
- 299-309
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC8008476
- OpenAlex
- W2988773550
- Cited by
- 2,770
- References
- 188
- Citations by year
- 2026: 344 · 2025: 533 · 2024: 524 · 2023: 467 · 2022: 397 · 2021: 346 · 2020: 150 · 2019: 4
- FWCI
- 21.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Eli Lilly and Company
- National Cancer Institute (R01CA207244, R01CA190642, P30CA008748, T32CA009207)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- chemoresistance, tumor heterogeneity, tumor microenvironment, tumor immune evasion, tumor growth kinetics, tumor burden, early cancer detection, adaptive monitoring, synthetic lethality screen, precision oncology
- MeSH terms
- Antineoplastic Agents, Humans, Models, Biological, Neoplasms, Drug Resistance, Neoplasm, Tumor Microenvironment
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