The DOI matches its Crossref record; 193 of the 196 references it cites were found in a registry or an index.
Molecular mechanisms of cisplatin resistance
Abstract
Platinum-based drugs, and in particular cis-diamminedichloroplatinum(II) (best known as cisplatin), are employed for the treatment of a wide array of solid malignancies, including testicular, ovarian, head and neck, colorectal, bladder and lung cancers. Cisplatin exerts anticancer effects via multiple mechanisms, yet its most prominent (and best understood) mode of action involves the generation of DNA lesions followed by the activation of the DNA damage response and the induction of mitochondrial apoptosis. Despite a consistent rate of initial responses, cisplatin treatment often results in the development of chemoresistance, leading to therapeutic failure. An intense research has been conducted during the past 30 years and several mechanisms that account for the cisplatin-resistant phenotype of tumor cells have been described. Here, we provide a systematic discussion of these mechanism by classifying them in alterations (1) that involve steps preceding the binding of cisplatin to DNA (pre-target resistance), (2) that directly relate to DNA-cisplatin adducts (on-target resistance), (3) concerning the lethal signaling pathway(s) elicited by cisplatin-mediated DNA damage (post-target resistance) and (4) affecting molecular circuitries that do not present obvious links with cisplatin-elicited signals (off-target resistance). As in some clinical settings cisplatin constitutes the major therapeutic option, the development of chemosensitization strategies constitute a goal with important clinical implications.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Also, constant or prolonged cisplatin treatment often results in the acquisition of resistance through the selection bias of alternative cell survival pathways, leading to therapeutic failure and poor prognosis [9, 10].”
From Advances in platinum-based cancer therapy: overcoming platinum resistance through rational combinatorial strategies (2025) · cites this paper as [9]
In the citing paper
“Mechanistically, cells can prevent cisplatin from reaching and harming DNA by reducing drug uptake, increasing drug efflux, and inactivating the drug through covalent binding to glutathione or metalloproteins [9, 10].”
From Advances in platinum-based cancer therapy: overcoming platinum resistance through rational combinatorial strategies (2025) · cites this paper as [9]
In the citing paper
“However, mitotic catastrophe appears to constitute a major mechanism of action of anticancer chemotherapeutics, mostly reflecting the increased resistance of neoplastic cells to the induction of intrinsic apoptosis [1004–1009].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [1007]
Citations
Cites
Studies of the HER-2/ neu Proto-Oncogene in Human Breast and Ovarian Cancer
Slamon, D. J., Godolphin, W. J., Jones, L. A., Holt, J. A., Wong, S., Keith, D. E., Levin, W. J., Stuart, S. G., Udove, J. A., Ullrich, A., et al. (1989) · Science · doi:10.1126/science.2470152 · Cited by 6,817
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Farmer, H., McCabe, N., Lord, C. J., Tutt, A. N. J., Johnson, D. A., Richardson, T. B., Santarosa, M., Dillon, K. J., Hickson, I., Knights, C., et al. (2005) · Nature · doi:10.1038/nature03445 · Cited by 6,683
Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
Bryant, H. E., Schultz, N., Thomas, H. D., Parker, K. M., Flower, D., Lopez, E., Kyle, S., Meuth, M., Curtin, N. J., & Helleday, T. (2005) · Nature · doi:10.1038/nature03443 · Cited by 5,198
The resurgence of platinum-based cancer chemotherapy
Kèlland, L. R. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2167 · Cited by 4,733
de Gramont, A., Figer, A., Seymour, M., Homerin, M., Hmissi, A., Cassidy, J., Boni, C., Cortes-Funes, H., Cervantes, A., Freyer, G., et al. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.16.2938 · Cited by 3,815
Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598
Self-citationAutophagy and the Integrated Stress Response
Kroemer, G., Mariño, G., & Levine, B. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.023 · Cited by 3,506
Self-citationCisplatin: mode of cytotoxic action and molecular basis of resistance
Siddik, Z. H. (2003) · Oncogene · doi:10.1038/sj.onc.1206933 · Cited by 3,335
Molecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints
Sancar, A., Lindsey-Boltz, L. A., Ünsal-Kaçmaz, K., & Linn, S. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073723 · Cited by 3,317
Calreticulin exposure dictates the immunogenicity of cancer cell death
Obeid, M., Tesniere, A., Ghiringhelli, F., Fimia, G. M., Apetoh, L., Perfettini, J.-L., Castedo, M., Mignot, G., Panaretakis, T., Casares, N., et al. (2007) · Nature Medicine · doi:10.1038/nm1523 · Cited by 3,216
Self-citation
Research works printed but not linked: 1
- Kato J, Kuwabara Y, Mitani M, Shinoda N, Sato A, Toyama T et al. (2001). Expression of survivin in esophageal cancer: correlation with the prognosis and response to chemotherapy. Int J Cancer 95: 92–95. · DOI
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Self-citationCisplatin: The first metal based anticancer drug
Ghosh, S. (2019) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2019.102925 · Cited by 1,816
Mitochondrial metabolism and cancer
Porporato, P. E., Filigheddu, N., Pedro, J. M. B., Kroemer, G., & Galluzzi, L. (2017) · Cell Research · doi:10.1038/cr.2017.155 · Cited by 1,323
Self-citationZeng, L., Gupta, P., Chen, Y., Wang, E., Ji, L., Chao, H., & Chen, Z. (2017) · Chemical Society Reviews · doi:10.1039/c7cs00195a · Cited by 1,027
Platinum-based drugs: past, present and future
Dilruba, S., & Kalayda, G. V. (2016) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-016-2976-z · Cited by 909
Metadata
- Authors
- Galluzzi, L., Senovilla, L., Vitale, I., Michels, J., Martins, I., Kepp, O., Castedo, M., & Kroemer, G.
- Affiliations
- Inserm (FR)
- Université Paris-Sud (FR)
- Corresponding author
- Kroemer, G
- Venue
- Oncogene
- Published
- 2011-09-05
- Volume
- 31
- Issue
- 15
- Pages
- 1869-1883
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2141037581
- Cited by
- 2,760
- References
- 196
- Citations by year
- 2026: 154 · 2025: 187 · 2024: 244 · 2023: 220 · 2022: 247 · 2021: 308 · 2020: 252 · 2019: 213 · 2018: 169 · 2017: 167 · 2016: 159 · 2015: 160 · 2014: 145 · 2013: 89 · 2012: 44
- FWCI
- 7.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission
- Ligue Contre le Cancer
- Fondation Bettencourt Schueller
- Labex Immuno-Oncology
- 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 resistance, chemoresistance, platinum anticancer drugs, DNA damage response, mitochondrial apoptosis, chemosensitization, DNA lesions
- MeSH terms
- Cisplatin, DNA Damage, DNA Repair, Humans, Signal Transduction, DNA Adducts, Drug Resistance, Neoplasm
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
