Cisplatin (CDDP)
Cisplatin (CDDP): Definition and Characteristics
What is Cisplatin?
Cisplatin (CDDP) is a platinum-based chemotherapeutic drug, first approved for clinical use in the 1970s, and remains one of the most widely utilized agents for treating solid tumors such as testicular, ovarian, bladder, cervical, lung, and head and neck cancers. Its enduring clinical significance is due to its potent DNA-damaging activity and proven efficacy, especially in highly curable malignancies like testicular cancer.
Characteristics
Mechanism of Action: Cisplatin exerts its cytotoxic effect mainly through the formation of covalent DNA adducts. After entering the cell, it undergoes aquation where chloride ligands are replaced by water molecules, allowing active cisplatin to bind to the N7 position of guanine bases in DNA. This binding results in intra- and inter-strand DNA crosslinks, distorting the DNA helix, interfering with replication and transcription, and triggering DNA damage response pathways.
Cellular Response: The accumulation of DNA lesions from cisplatin leads to cell cycle arrest (often at the G2/M checkpoint) and activation of apoptosis (programmed cell death), mainly in rapidly dividing cells. Secondary cytotoxic effects include the generation of reactive oxygen species, mitochondrial dysfunction, and activation of stress signaling pathways.
Clinical Use: Cisplatin is foundational in oncology protocols and is included in treatment guidelines such as those from NCCN and ESMO. It is most effective against rapidly proliferating tumors, but its use is limited by significant toxicity, including nephrotoxicity, neurotoxicity, and ototoxicity, as well as emerging drug resistance.
Factors Contributing to Cell Death: Cellular context, such as p53 status and mismatch repair system integrity, greatly affects cisplatin’s efficiency and resistance, with alterations in drug uptake/efflux and DNA repair mechanisms contributing to chemoresistance.
Clinical Significance
Efficacy: Cisplatin remains a cornerstone in cancer therapy due to high response rates in several solid tumors.
Toxicity: Major side effects may include kidney damage, hearing loss, nerve dysfunction, and other systemic toxicities; these can limit treatment duration and dosage.
Resistance: Cancer cells may develop resistance through increased DNA repair, altered cisplatin transport, or changes in apoptosis regulatory proteins, sometimes necessitating combination therapy with other anticancer agents.
Etymology
The name “cisplatin” derives from its chemical structure: “cis” (denoting the arrangement of ammine and chloride ligands on the same side of the platinum ion) and “platinum”.
Key Points
Cisplatin is a platinum-based chemotherapy agent essential for treating various cancers.
It works by entering cells and binding to DNA, causing crosslinks that lead to cell death through apoptosis.
Primary limitations are significant side effects and acquired drug resistance.
Ongoing research focuses on optimizing delivery, minimizing toxicity, and overcoming resistance.
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For guidance on cisplatin-based chemotherapy or management of treatment-related complications, our oncology specialists provide evidence-based advice and personalized care strategies including Cellular Immunotherapies.
References:
Biomed Pharma Journal. Review on Pharmacology of Cisplatin: Clinical Use, Toxicity and Mechanism of Resistance of Cisplatin. 2019.biomedpharmajournal
OncoDaily. Cisplatin in Cancer Treatment: Mechanism, Resistance, Toxicity and Best Practices. 2025.oncodaily
PubMed. Cisplatin biochemical mechanism of action. 2003.pubmed.ncbi.nlm.nih
DovePress. Advances in Our Understanding of the Molecular Mechanisms of Action of Cisplatin. 2021.dovepress
PubMed Central. Cisplatin in cancer therapy: molecular mechanisms of action. 2014.pmc.ncbi.nlm.nih
ScienceDirect. Cisplatin in cancer therapy. 2014.sciencedirect
DrugBank. Cisplatin: Uses, Interactions, Mechanism of Action. 2023.drugbank
Wikipedia. Cisplatin. 2005.wikipedia
JPCCR. Pharmacological profile and clinical features of cisplatin. 2009.jpccr
