Abstract
Abstract
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children with two subtypes: embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma (ARMS). With current treatment strategies, most children with recurrent or high-risk disease fare poorly, identifying a need for novel therapeutic approaches. The novel retinoid, ST1926, is an orally available compound belonging to the class of synthetic atypical retinoids and is currently in clinical trials. ST1926 is showing promise because of its increased specificity and reduced toxicity and its unique antitumor mechanism of action that appears different from that of classical all-trans retinoic acid (ATRA). We are investigating the therapeutic potential of this novel synthetic retinoid ST1926, in treatment of RMS. Cell viability assessed by MTT assay showed that ST1926 was a much more potent inhibitor of cell proliferation than ATRA, in both ERMS and ARMS cell lines in vitro. In fact, ST1926 effectively inhibited cell proliferation in all tested cell lines, at concentrations as low as 0.5 micromolar, which is easily achievable in vivo. Unlike ATRA, ST1926 did not induce morphological differentiation in RMS cells. Further analysis showed that ST1926 induced accumulation of cells in S and/or in G2/M phases of the cell cycle, as well as induction of apoptosis in some cell lines, in a p53-independent manner. We are currently investigating the mechanistic details of the cell cycle inhibitory activities of ST1926 in RMS cells. This data identifies ST1926 as an interesting possible therapeutic agent in RMS, and in vivo preclinical studies utilizing this agent are currently underway.
Citation Format: Hussein Basma, Loai Dweik, Nadine Darwiche, Claudio Pisano, Raya Saab. The novel atypical retinoid ST1926 is active against rhabdomyosarcoma and induces cell cycle arrest in S and G2/M phases. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr A39.