Abstract 5381: Therapeutic potential of HDAC inhibitors in small cell carcinoma of the ovary, hypercalcemic type (SCCOHT)

SCCOHT is a rare but deadly type of ovarian cancer. It mainly affects young women with the median age about 28 years. Although often diagnosed at an early stage, the prognosis of SCCOHT is nonetheless dismal with a 2-year survival less than 35% due to lack of effective treatments. Unlike common malignancies, the genome of SCCOHT is minimally disturbed. Recently, we and others have discovered inactivating mutations of SMARCA4, the ATPase of the SWI/SNF chromatin remodeling complex, in the majority of SCCOHT along with loss of SMARCA4 protein. Interestingly, SMARCA2, the alternative ATPase of the SWI/SNF complex is also inactivated in SCCOHT without apparent mutations. Re-expression of either SMARCA4 or SMARCA2 robustly inhibited the growth of SCCOHT cells. Therefore, the dual deficiency of SMARCA4 and SMARCA2 may be the primary driver in SCCOHT tumorigenesis by creating distinct epigenetic features that promote oncogenic transformation and can serve as promising therapeutic targets. In an attempt to identify epigenetic drugable targets, we performed the drug screening using an epigenetic drug library (Cayman Chemical) in two SCCOHT cell lines and four other ovarian cancer cell lines with intact SMARCA4 and SMARCA2. We identified several HDAC inhibitors that selectively inhibited the viability of SCCOHT cells (BIN67 and SCCOHT1) compared to that of other ovarian cancer cell lines. We confirmed that in comparison to other ovarian cancer cell lines, SCCOHT cells were significantl...

Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Wang, Y., Ramos, P., Karnezis, A. N., Trent, J. M., Huntsman, D. G. Tags: Experimental and Molecular Therapeutics Source Type: research