Mechanisms of Cancer Drug Resistance
Abstract
▪ Abstract The design of cancer chemotherapy has become increasingly sophisticated, yet there is no cancer treatment that is 100% effective against disseminated cancer. Resistance to treatment with anticancer drugs results from a variety of factors including individual variations in patients and somatic cell genetic differences in tumors, even those from the same tissue of origin. Frequently resistance is intrinsic to the cancer, but as therapy becomes more and more effective, acquired resistance has also become common. The most common reason for acquisition of resistance to a broad range of anticancer drugs is expression of one or more energy-dependent transporters that detect and eject anticancer drugs from cells, but other mechanisms of resistance including insensitivity to drug-induced apoptosis and induction of drug-detoxifying mechanisms probably play an important role in acquired anticancer drug resistance. Studies on mechanisms of cancer drug resistance have yielded important information about how to circumvent this resistance to improve cancer chemotherapy and have implications for pharmacokinetics of many commonly used drugs.
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The majority of patients who respond well to initial targeted cancer therapy develop resistance.
“This is not surprising, since decades of research on targeted cancer therapy have shown that the majority of patients who respond well to initial treatment develop resistance.57, 58, 59, 60”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [60]
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- Authors
- Gottesman, M. M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Gottesman, Michael M.
- Venue
- Annual Review of Medicine
- Publisher
- Annual Reviews
- Published
- 2002-02
- Volume
- 53
- Issue
- 1
- Pages
- 615-627
- ISSN
- 0066-4219 (ISSN-L)
- 1545-326X
- OpenAlex
- W2169302611
- Cited by
- 2,643
- References
- 1
- Citations by year
- 2026: 59 · 2025: 97 · 2024: 86 · 2023: 109 · 2022: 116 · 2021: 134 · 2020: 165 · 2019: 169 · 2018: 165 · 2017: 188 · 2016: 174 · 2015: 208 · 2014: 219 · 2013: 139 · 2012: 119
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
- Keywords
- chemoresistance, acquired drug resistance, intrinsic drug resistance, multidrug resistance, drug detoxification, tumor genetic heterogeneity, pharmacokinetics, chemotherapy
- MeSH terms
- Animals, Antineoplastic Agents, Cell Survival, Humans, Inactivation, Metabolic, Neoplasms, Apoptosis, Drug Resistance, Neoplasm
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