SUMMARY OF INVENTION
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the third-leading cause of cancer-related mortality worldwide. The MYC oncoprotein, amplified in ~33% of hepatocellular carcinomas, is a well-validated but currently undruggable driver of HCC. Overexpression of MYC causes uncontrolled cell proliferation by affecting multiple cellular processes including gene transcription, DNA replication, and protein translation.
Through an RNAi screen, MSK investigators identified CDK9 (cyclin-dependent kinase 9) as required for proliferation of MYC-overexpressing liver tumors. Furthermore, MSK investigators found that liver tumors which overexpress MYC are sensitive to CDK9 inhibitor treatment, while liver tumors with normal MYC expression levels are less sensitive to CDK9 inhibitor treatment. Therefore, CDK9 inhibitors could be used to treat liver cancers, and potentially other tumor types, which have elevated levels of MYC.
- Detection of amplified MYC could be used to predict response to CDK9 inhibitor therapy in liver cancers and potentially other tumor types
- Utilizing amplified MYC as a biomarker to select for patients eligible for treatment with CDK9 inhibitors could expand the number of patients who could benefit from treatment with this class of therapies
Hepatocellular carcinoma is the most common type of primary liver cancer, and its incidence rate continues to increase. In 2016, there will be an estimated ~35K new cases of HCC in the U.S., and there are over ~55K patients currently living with liver cancer in the U.S.
Huang C-H. et al., CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma. Genes and Development, 28(16), 2015 (PubMed ID: 25128497)
AREAS OF APPLICATION
Initial application of hepatocellular carcinoma (HCC), with potential expansion to include other tumor types with elevated levels of MYC
STAGE OF DEVELOPMENT
In vivo data
U.S. National 10,383,873 issued Aug. 20, 2019. U.S. Divisional 16/544,180 pending; EUR National published; National applications pending in Canada, France, Germany, Italy, Spain, and U.K.
Scott Lowe, PhD, Chair and Laboratory Head, Cancer Biology and Genetics Program, Sloan Kettering Institute, MSK