Research And Grants

Dual targeting processive transcription for Myc-driven circuitry in medulloblastoma.

Medulloblastomas (MB) are the most common brain cancer in children.  The highest-risk subgroups are defined by elevated expression of a protein called Myc (Myc-MB) and exhibit high rates of metastasis and disease recurrence, resulting in unacceptable long-term survival rates of less than 30%. The Myc protein itself has proven challenging to target directly with medications.  As a result, a better understanding of the mechanisms surrounding Myc expression and action within MB cells will not only reveal fundamental new insights into cancer biology, but it may identify new ways to leverage drugs against this system.

We have identified regulatory proteins called CDK7 and CDK9 that are required for Myc expression and activity.  Unlike Myc, new generations of targeted inhibitors against these proteins are already in clinical trials.  Our research has shown that these agents are highly effective against Myc-MB.  This project examines how Myc-MB are dependent on these proteins for survival and how new inhibitors can be used to exploit this dependency.  We are already developing our lead agent, zotiraciclib, in a clinical trial for other childhood brain tumors.  If successful, this proposal would enable the rapid translation of this agent into phase 1 trials for children with high-risk medulloblastoma.