SBIR Diagnostic Method to Identify approved drugs as treatment options in individuals with rare cancer

这项建议的长期目标是改善一线环境下卵巢癌患者的预后。 卵巢癌和其他罕见癌症的有效药物治疗选择很少，而300多种药物已经 被FDA批准用于治疗非罕见癌症。对肿瘤基因表达的分析有可能识别 被批准的药物靶点的过度表达，如HER2、AR和PD-L1，以及使 卵巢肿瘤对PARP抑制剂更敏感。 在这个项目中，一种名为“OneRNA”的专利肿瘤信使核糖核酸测序方法将在30年内得到分析验证 通过(1)比较相对mRNA表达水平(肿瘤与正常)和 逆转录酶聚合酶链式反应(RT-PCR)(2)评估异常表达基因与 OneRNA检测采用FDA批准的免疫组织化学(IHC)检测。根据初步数据，我们预计 在90%以上的肿瘤中确定至少一个临床可操作的异常表达基因。 所得到的数据将支持由基因组表达公司推出的卵巢肿瘤表达分析服务 CLIA实验室帮助肿瘤学家确定哪些药物和药物组合可能使卵巢癌患者受益。

The long term objective of this proposal is to improve outcomes for ovarian cancer patients in the frontline setting. Few effective drug treatment options exist for ovarian cancer and other rare cancers whereas 300+ drugs have been approved by the FDA to treat non-rare cancers. Analysis of tumor mRNA gene expression has the potential to identify over expression of approved drug targets, such as HER2, AR, and PD-L1, and silencing of DNA repair genes that make ovarian tumors more responsive to PARP inhibitors. In this project, a proprietary tumor mRNA sequencing method called “OneRNA” will be analytically validated in 30 clinically annotated de-identified ovarian tumors by (1) comparing relative mRNA expression levels (tumor vs normal) to reverse transcriptase PCR (RT-PCR) (2) evaluating concordance of aberrantly expressed genes detected with the OneRNA assay with FDA approved immunohistochemical (IHC) assays. Based on preliminary data, we expect to identify at least one clinically actionable aberrantly expressed gene in over 90% of tumors. The resulting data will support the launch of an ovarian tumor expression analysis service by the Genomic Expression CLIA lab to help oncologists identify which drugs and drug combinations are likely to benefit ovarian cancer patients.