Description:
Researchers at TGen, in collaboration with the University of British Columbia, have developed methods and compositions for screening for Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT) in a patient based on the genomic profile of a biological sample to enable earlier diagnosis and more effective treatment than is currently available for SCCOHT patients. Methods of treating SCCOHT were also developed based on the target gene mutation that was discovered through this collaborative research, providing an alternative to the current treatment methods that have provided only limited success.
SCCOHT is a rare and highly aggressive form of ovarian cancer that affects female young adults and adolescents, with most SCCOHT patients being diagnosed at an advanced stage where surgery followed by chemotherapy and/or radiation or autologous stem cell transplantation have not been successful as treatment courses. As a result, more than 75% of patients succumb to their disease within 1-2 years. Previous research provided little information on the molecular biology of these rapidly dividing tumors to guide the development of therapies for SCCOHT patients. While SCCOHT has been shown to be distinguished from more common types of ovarian cancer and small cell carcinomas by its histological appearance, immunoprofile, and cytogenetic characteristics, the previous research did not provide a genomic and pathologic assessment to effectively screen for SCCOHT or a predisposition to SCCOHT.
Through the molecular characterization of SCCOHT tumors, the researchers identified an inactivating alteration in the SWI/SNF complex, particularly in the SMARCA4 gene. The identification of inactivating SMARCA4 mutations in almost all cases of SCCOHT provides a significant insight into the pathogenesis of the disease to differentiate SCCOHT from other more common ovarian carcinomas, and offers the opportunity for genetic testing of family members at risk. Additionally, the detection of this germline and somatic SMARCA4 gene mutation allows for effective treatment strategies to be developed and implemented which have a higher probability of impact than available treatment strategies. These new treatment strategies include treating with: an inhibitor of a target gene that is synthetic lethal with the SMARCA4 gene, SMARCA4 gene or protein replacement therapy, and/or a SMARCA4 protein mimetic. Further treatments may include treating with an epigenetic agent, a fibroblast growth factor receptor (FGFR) inhibitor, and/or a receptor tyrosine kinase (RTK) of the TYRO3/AZL/MerTK family (MERTK) inhibitor.
Link to Published US Patent Application 2017/0107578 A1
