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Bonnie Lau

Bonnie Lau, M.D., Ph.D.

Assistant Professor of Pediatrics

Datmouth-Hitchcock Clinic

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Combining PARP inhibitor with Standard Chemotherapy for Childhood Acute Myeloid Leukemia

Leukemia is the most common cancer in childhood and has been subject to decades of research and improved therapies. While certain types of leukemia have a >95% chance of cure with these improved therapies, another type of leukemia, acute myeloid leukemia (AML), continues to have poor prognosis with a survival rate <65%. Part of the decreased treatment success is due to AML tumor cells being resistant to being killed by current chemotherapies. Many standard chemotherapy agents work to kill tumor cells by inducing DNA damage, and the tumor cell subsequently dies because the tumor cell cannot divide and grow when the DNA damage persists.

First, we will assess for increased DNA damage from combining a novel DNA-damaging drug called a PARP inhibitor, with standard chemotherapy agents. Not only can combination therapy be more effective than single agent therapy, but also combination therapy can overcome therapy resistance, which is a cause of poor outcomes in childhood AML.

We will also test our hypothesis for effectiveness in treating childhood AML by testing human AML tumor cells in a humanized mouse model, an innovative model for looking at human AML in an organism rather than in a lab dish. This murine model will help us determine the most effective therapies to use in combination with PARP inhibitor, and also start looking at the safety of using these drug combinations. The outcomes of these findings would greatly benefit children with AML to have more options for therapy to achieve cure.

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