Wiktoria Pacuła, Zuzanna Rogacz, Kacper Kalarus, Ilona Nowak, Barbara Strzałka-Mrozik
Oxaliplatin: Mechanism of Action, Clinical Applications, and Development Perspectives
2025-10-31
Subject of Study. This paper presents oxaliplatin, a third-generation platinum-based chemotherapeutic agent widely used in the treatment of various cancers, including colorectal, ovarian, gastric, and lung cancers. Its distinct pharmacological profile is attributed to the presence of the DACH ligand, which differentiates it from cisplatin and carboplatin.
The mechanism of action of oxaliplatin involves the formation of stable DNA adducts that inhibit replication and transcription. Compared to cisplatin, oxaliplatin-derived adducts are more stable and induce greater DNA helix distortion. These lesions are primarily repaired via the nucleotide excision repair (NER) pathway.
Following internalization, the drug is activated, forming reactive platinum complexes that interact with nucleophilic cellular components such as DNA, RNA, and proteins. Clinically, oxaliplatin is an integral component of combination chemotherapy regimens such as FOLFOX and CAPOX, both of which have well-documented efficacy.
Current research on oxaliplatin focuses on optimizing treatment protocols by combining it with other anticancer agents to enhance therapeutic efficacy, reduce toxicity, and overcome tumor resistance.
Research objective. The aim of this study is to present the properties of oxaliplatin, its molecular mechanisms of action, clinical applications, and potential therapeutic prospects.
Literature search and selection methodology. The literature review was based on scientific materials obtained from databases such as PubMed, ResearchGate, Google Scholar, the Northern Cancer Alliance, and the National Health Service. The following keywords were used in the search: “oxaliplatin,” “cis-[oxalato(trans-l-1,2 diaminocyclohexane)platinum(II)],” “chemotherapy,” “colon cancer,” “oxaliplatin mechanism of action,” “oxaliplatin toxicity,” “oxaliplatin chemotherapy regimens,” “CAPOX,” “FOLFOX,” and “oxaliplatin resistance.”
Results. Oxaliplatin, used in FOLFOX and CAPOX regimens for colorectal cancer treatment, is associated with characteristic adverse effects such as peripheral neuropathy, myelosuppression, and hypersensitivity reactions. Additional side effects include fatigue, gastrointestinal toxicity, and splenomegaly.
Ongoing clinical studies focus on modifying treatment protocols and introducing supportive therapies, as well as identifying mechanisms of oxaliplatin resistance. Resistance to the drug is complex and may result from decreased intracellular accumulation of oxaliplatin, enhanced detoxification processes, efficient DNA repair mechanisms, evasion of apoptosis, and epigenetic alterations. Current strategies to counteract resistance involve inducing autophagy, reducing glutathione levels, and inhibiting specific signaling pathways, which may restore the sensitivity of cancer cells to oxaliplatin therapy.
Conclusions. Oxaliplatin exhibits a unique antitumor mechanism, particularly effective in the treatment of colorectal cancer, through the formation of stable DNA adducts that disrupt replication and transcription processes. Its distinct toxicity profile compared to cisplatin and carboplatin allows for its use in patients who have contraindications to earlier generations of platinum-based drugs. Current research on oxaliplatin focuses on combination therapies with EGFR inhibitors, gene therapy, and immunotherapy. Understanding the mechanisms of tumor resistance to oxaliplatin is also crucial, as it may contribute to the development of therapeutic strategies that enhance treatment efficacy and improve patient prognosis. A review of the literature concerning oxaliplatin’s activity in both in vitro and in vivo models indicates substantial grounds for continued research on this drug.
Keywords: oxaliplatin, chemotherapy, cancer.
© Farm Pol, 2025, 81(2): 99–112
