Evolution of platinum resistance in high-grade serous ovarian cancer
Abstract
High-grade serous ovarian cancers account for most ovarian-cancer mortality. Although this disease initially responds well to platinum-based chemotherapy, relapse and progression to chemotherapy resistance are frequently seen. Time to relapse after first-line therapy is a predictor of response to secondary platinum treatment: more than 12 months is associated with high chance of a secondary response, whereas relapses within 6 months generally indicate platinum resistance. In this Personal View we discuss whether patterns of response, relapse, and the development of drug resistance in high-grade serous ovarian cancers are related to distinct underlying molecular and cellular biological characteristics. In particular, we propose that rapid relapse with platinum-resistant disease is due to minor subpopulations of intrinsically resistant cancer cells at presentation.
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Up to 75% of ovarian cancer patients who initially respond to therapy relapse, and effective second line treatment therapies are lacking.
“In addition, up to 75% of patients who initially respond to therapy, relapse and effective second line treatment therapies are lacking (Harries and Kaye, 2001; Cooke and Brenton, 2011; Brooks et al., 2019).”
From Microphysiological systems as models for immunologically ‘cold’ tumors (2024) · cites this paper as Cooke and Brenton, 2011
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Tumour‐associated macrophages act as a slow‐release reservoir of nano‐therapeutic Pt(IV) pro‐drug
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Self-citationMicrophysiological systems as models for immunologically ‘cold’ tumors
Gaebler, D., Hachey, S. J., & Hughes, C. C. W. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1389012 · Cited by 12 · see citing works
- Authors
- Cooke, S. L., & Brenton, J. D.
- Affiliations
- Cancer Research UK (GB)
- Corresponding author
- Brenton, James D
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 12
- Issue
- 12
- Pages
- 1169-1174
- ISSN
- 1470-2045 (ISSN-L)
- OpenAlex
- W2039785378
- Cited by
- 213
- References
- 8
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 18 · 2023: 12 · 2022: 7 · 2021: 20 · 2020: 18 · 2019: 12 · 2018: 15 · 2017: 14 · 2016: 15 · 2015: 20 · 2014: 15 · 2013: 8 · 2012: 9
- FWCI
- 12.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research UK (15601)
- University of Cambridge
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- high-grade serous ovarian cancer, platinum resistance, chemoresistance, relapse, time to relapse, tumor heterogeneity
- MeSH terms
- Female, Humans, Organoplatinum Compounds, Ovarian Neoplasms, Time Factors, Treatment Failure, Platinum Compounds, Neoplasms, Cystic, Mucinous, and Serous, Disease Progression, Drug Resistance, Neoplasm, Neoplasm Grading
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