June 2019

Laboratory Research Grant for Elizabeth Beierle, University of Alabama at Birmingham

Hepatoblastoma (HB) is the most common primary liver tumor in children and its incidence is rising. Although survival rates for pediatric cancers have improved dramatically in the past 30 years, HB remains one of the most difficult childhood tumors to treat. Many children have disease that is resistant to standard treatments that will require novel, innovative, and targeted combinatorial therapies to effectively treat or manage their disease. We plan to demonstrate a driver role for a protein known as PIM3 kinase as a mechanism for HB chemotherapy resistance and recurrence. PIM3 is known to affect cancer growth in adult liver cancer and we have found that PIM3 is expressed in pediatric HB tumor specimens. Further, inhibition of PIM3 resulted in decreased HB tumor cell survival and tumor growth in animals. We believe that there is a small population of cells, called tumor initiating cells, which contribute to chemotherapy resistance and cancer relapse. We have made the novel observation that PIM3 affects this distinct population of HB cells and may render them more susceptible to chemotherapy. The aims of the proposed studies are to show that PIM3 does play a role in the maintenance of this special cell population and that targeting PIM3 results in decreased resistance to standard chemotherapies. We will use cultured HB cells and animals’ models to study these aims. The expected findings will be particularly exciting since there are inhibitors available and currently in clinical trials for PIM3 that could be rapidly advanced for use in pediatrics.

Few options exist for recurrent or resistant hepatoblastomas, and basic laboratory research must first be established and advanced to create clinical trials for children. This research funding enables Elizabeth Beirele’s first-of-its-kind postulation to be further developed in her lab in Alabama, bringing it closer to the important goal of treating children in the clinic. [$50,000]

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