Cellular processing of platinum anticancer drugs
Abstract
Cisplatin, carboplatin and oxaliplatin are platinum-based drugs that are widely used in cancer chemotherapy. Platinum-DNA adducts, which are formed following uptake of the drug into the nucleus of cells, activate several cellular processes that mediate the cytotoxicity of these platinum drugs. This review focuses on recently discovered cellular pathways that are activated in response to cisplatin, including those involved in regulating drug uptake, the signalling of DNA damage, cell-cycle checkpoints and arrest, DNA repair and cell death. Such knowledge of the cellular processing of cisplatin adducts with DNA provides valuable clues for the rational design of more efficient platinum-based drugs as well as the development of new therapeutic strategies.
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In rat kidney proximal tubular cells, cisplatin induces MSH2-mediated and ATR-dependent phosphorylation of p53 at serine 15 and Chk2 at threonine 68.
“cisplatin induces MSH2-mediated and ATR-dependent p53 phosphorylation at Serine 15 and Chk2 phosphorylation at Threonine 68 in rat kidney proximal tubular cells.”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [215]
An MMR protein participates in ATR activation after cisplatin-induced oxidative stress.
“This suggests the involvement of a MMR protein in ATR activation in response to cisplatin-induced oxidative stress [215, 216].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [215]
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- Authors
- Wang, D., & Lippard, S. J.
- Affiliations
- Massachusetts Institute of Technology (US)
- Corresponding author
- Lippard, Stephen J.
- Venue
- Nature Reviews Drug Discovery
- Published
- 2005-03-24
- Volume
- 4
- Issue
- 4
- Pages
- 307-320
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- OpenAlex
- W1974693247
- Cited by
- 3,801
- References
- 230
- Citations by year
- 2026: 109 · 2025: 132 · 2024: 178 · 2023: 177 · 2022: 196 · 2021: 235 · 2020: 240 · 2019: 226 · 2018: 235 · 2017: 249 · 2016: 222 · 2015: 205 · 2014: 216 · 2013: 205 · 2012: 198
- FWCI
- 10.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Oncology › Metal complexes synthesis and properties
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
- Keywords
- cisplatin, carboplatin, oxaliplatin, platinum anticancer drugs, platinum-DNA adducts, drug uptake, DNA damage signaling, cell cycle checkpoints, DNA repair, cell death, cytotoxicity, rational drug design
- MeSH terms
- Animals, Antineoplastic Agents, Cell Survival, DNA Damage, DNA Repair, Humans, Organoplatinum Compounds, Tumor Cells, Cultured, Molecular Structure, Signal Transduction, Apoptosis
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