Cited by 2,770Cancer Cells and MetastasisDrug Transport and Resistance MechanismsCancer Genomics and Diagnostics

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A view on drug resistance in cancer

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Vasan, Neil, Baselga, José, Hyman, David M.·2019·Nature

DOI 10.1038/s41586-019-1730-1PMC PMC8008476

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Abstract

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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Authors: Vasan, N., Baselga, J., & Hyman, D. M.
Affiliations: Memorial Sloan Kettering Cancer Center (US)
Corresponding author: Hyman, David M.
ORCID: Vasan, Neil
Hyman, David M.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2019-11-13
Volume: 575
Issue: 7782
Pages: 299-309
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/s41586-019-1730-1
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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