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Supplement

Trabectedin mechanism of action and platinum resistance: molecular rationale

    Isabelle Ray-Coquard

    *Author for correspondence:

    E-mail Address: isabelle.ray-coquard@lyon.unicancer.fr

    Département de Cancérologie Médicale, Centre Léon Bérard, Lyon, France

    Search for more papers by this author

    Published Online:11 Oct 2017https://doi.org/10.2217/fon-2017-0318

    Abstract

    Trabectedin presents a complex mode of action affecting key cell biology processes in tumor cells and in the tumor microenvironment. In ovarian cancer patients with a platinum treatment-free interval of 6–12 months treated with trabectedin + pegylated liposomal doxorubicin (PLD) or single-agent PLD, and retreated with platinum after relapse, overall survival was significantly prolonged in the trabectedin + PLD group. Mechanisms by which trabectedin restores tumor sensitivity to platinum include its interaction with components of the nucleotide excision repair machinery in tumor cells and inhibition of inflammatory mediators such as IL-6 in the tumor microenvironment. Additionally, BRCA mutations and associated homologous recombination repair deficiency may contribute to enhanced sensitivity to trabectedin observed in BRCA-mutated patients with ovarian cancer.

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