Geldanamycin treatment does not result in anti-cancer activity in a preclinical model of orthotopic mesothelioma

M. Lizeth Orozco Morales, Catherine A. Rinaldi, Emma de Jong, Sally M. Lansley, Y. C.Gary Lee, Rachael M. Zemek, Anthony Bosco, Richard A. Lake, W. Joost Lesterhuis

Research output: Contribution to journalArticlepeer-review

Abstract

Mesothelioma is characterised by its aggressive invasive behaviour, affecting the surrounding tissues of the pleura or peritoneum. We compared an invasive pleural model with a noninvasive subcutaneous model of mesothelioma and performed transcriptomic analyses on the tumour samples. Invasive pleural tumours were characterised by a transcriptomic signature enriched for genes associated with MEF2C and MYOCD signaling, muscle differentiation and myogenesis. Further analysis using the CMap and LINCS databases identified geldanamycin as a potential antagonist of this signature, so we evaluated its potential in vitro and in vivo. Nanomolar concentrations of geldanamycin significantly reduced cell growth, invasion, and migration in vitro. However, administration of geldanamycin in vivo did not result in significant anti-cancer activity. Our findings show that myogenesis and muscle differentiation pathways are upregulated in pleural mesothelioma which may be related to the invasive behaviour. However, geldanamycin as a single agent does not appear to be a viable treatment for mesothelioma.
Original languageEnglish
Article numbere0274364
JournalPLoS One
Volume18
Issue number5
DOIs
Publication statusPublished - May 2023

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