Introduction: The synergistic combination of histone deacetylase inhibitors and platinum-based medicines represents a promising therapeutic strategy to efficacy and overcome drug resistance in cancer therapy, necessitating a comprehensive understanding on their molecular interactions and clinical potential.

Areas Covered: The objective of presented review is to investigate the molecular pathways of platinum medicines and HDAC inhibitors. A comprehensive literature review from 2011 to 2024 was conducted across multiple databases like MEDLINE, PubMed, Google Scholar, Science Direct, Scopus and official websites of ClinicalTrial.gov to explore publications on HDAC inhibitors, platinum drugs, and combination cancer therapies, revealing preliminary evidence of innovative treatment strategies involving HDAC inhibitors and platinum chemotherapeutics. Several new platinum (IV) complexes, with HDAC inhibitory moieties and better cytotoxicity profiles than conventional platinum drugs, are also reviewed here.

Expert Opinion: The above combination has great potential in cancer treatment, however managing toxicity, dosage regimens, and patient selection biomarkers are problematic. More selective HDAC inhibitors and innovative delivery techniques are potential areas for future research. An adaptation toward changing cancer therapeutic landscapes, highlights combining HDAC inhibitors with platinum-based medicines serves as a new concept for personalized medicine, however, a deeper research is still needed at this time.

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http://dx.doi.org/10.1080/14737140.2025.2458156DOI Listing

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