Novel Biomarker to Predict Response to CDK9 Inhibitors

SK2013-089

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.

ADVANTAGES

  • 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

     

MARKET OPPORTUNITY

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.

PUBLICATION

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

PATENT INFORMATION

PCT application (PCT/US2015/024057) filed on April 2, 2015

LEAD INVESTIGATOR

Scott Lowe, PhD, Chair and Laboratory Head, Cancer Biology and Genetics Program, Sloan Kettering Institute, MSK

CONTACT INFORMATION

Eileen Flowers, PhD

Licensing Manager
Tel: 646-888-1067
E-mail: flowerse@mskcc.org

Stage of Development

In vitro

Indications