Targeting Eya2 to Inhibit c-Myc driven Medulloblastoma Tumor Progression
Medulloblastoma is a deadly pediatric brain cancer. Although there are different types of medulloblastoma, patients are uniformly treated with therapies including surgery, radiation and chemotherapy. To find better treatments with less severe side effects, it is important to understand the different types of medulloblastoma so we can tailor the treatment to each subtype. Group3 medulloblastoma was identified because this subgroup of patients has extremely high levels of a gene called c-Myc in their tumors. c-Myc helps cell growth during development. In cancer, the same developmental processes are turned on and allow the tumor to quickly grow and become more aggressive. Therefore, it is not surprising that patients with Group 3 medulloblastoma, which has high c-Myc levels, have the worst survival rate when compared to other medulloblastoma subgroups.
To identify novel therapeutics for children with c-Myc driven medulloblastoma, we will investigate the role of the developmental protein Eya2. It can partner with another developmental protein Six1 or act by itself to control c-Myc levels. Understanding if and how Eya2 and/or Six1 promotes tumor growth in Group3 medulloblastoma, will help us develop and test our novel Six1/Eya2 interaction inhibitors (currently under development in our laboratory) in this devastating disease. We are excited to target the Eya2/Six1 complex with our inhibitors because Eya2 and/or Six1 are excellent therapeutic targets since these genes are only turned on in tumors and not in normal healthy tissues. They provide a novel therapeutic option that avoids the debilitating side effects that occur from current treatments
"With the financial support from the ALSF foundation, I am able to continue researching my passion of discovering new drug targets for a deadly childhood brain cancer known as medulloblastoma. By funding this project, ALSF is helping pave the way for the advancement of cutting edge science in discovering innovative treatment options for children with brain cancer. Thanks, ALSF!" - Melanie Vincent, PhD
Project Update 2020
To identify novel therapeutics for children with c-Myc driven medulloblastoma (Group 3), we have investigated the role of a developmental protein known as Eya2. Eya2 is highly expressed in Group3 medulloblastoma patients. Excitingly, our preliminary data show that targeting Eya2 may provide a new means to inhibit c-Myc expression in these tumors, which is the driving force of this cancer. We are collaborating with investigators at A*STAR to develop Eya2 small molecule inhibitors with better drug-like qualities so that we can test them in animal models. We are excited to target Eya2 with our inhibitors because Eya2 is an excellent therapeutic target for these patients since Eya2 is only turned on in the tumor and not in normal healthy tissues. Thus, they may provide a novel therapeutic option that avoids the debilitating side effects that occur from currently available treatments.