A Systems Biology Approach to Investigate the Mechanism of Action of Trabectedin in a Model of Myelomonocytic Leukemia .www.nature.com // The Pharmacogenomics Journal advance online publication, 13 December 2016 .
Yondelis It has a complex mode of action involving DNA repair and transcription mechanisms, resulting in cytotoxic effects with perturbations of the cell cycle and cell death (D'Incalci et al., for a review). Previous studies have indicated that trabectedin is cytotoxic not only against cancer cells, but exerts also a selective activity against monocytes and macrophages.
This finding was of interest as macrophages are quiescent cells generally considered very resistant to most anticancer drugs.
These observations led to discover that trabectedin has the ability to modulate the tumor microenvironment, that was proposed to be relevant also for its antitumor activity.
Recently, the drug has shown a significant cytotoxic activity against Juvenile and Chronic myelomonocytic cells taken from patients suffering from these diseases for which there is an urgent need of novel effective therapies.
This observation prompted us to investigate the mode of action of trabectedin in a representative myelomonocytic leukemia cell line. We have applied a systems biology approach to study gene expression profiles of treated cells integrated with specific experiments aimed at assessing their phenotype.
The results indicate that the drug has the ability to modulate specific pathways regulating cell cycle and cell death of myelomonocyctic leukemic cells, thus reinforcing the idea that the drug has potential therapeutic action against myelomonocytic leukemias.
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