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Precision Medicine Inhibitor and Immunotherapy Approaches for High-Risk Childhood Leukemias

Sarah Tasian

Sarah Tasian

MD

The Children's Hospital of Philadelphia

Project Term: October 1, 2021 - September 30, 2026

Dr Tasian’s scientific passion is successful development of precision medicine therapies for high-risk childhood leukemia.Her translational laboratory research program focuses upon investigation of kinase inhibitors and chimeric antigen receptor (CAR) T cell immunotherapies in childhood ALL and AML using primary patient specimens and patient-derived xenograft models.Through her laboratory and clinical research, she aspires to improve cure rates and minimize toxicities for children with leukemia.

Lay Abstract

While most children with acute leukemias can be cured with modern chemotherapy, outcomes for those who relapse or are resistant to chemotherapy remain dismal. Successful development of targeted treatment approaches that attack the ‘Achilles heels’ of leukemia cells or that work in different ways from conventional chemotherapy remains a critical need in pediatric oncology. During the past decade, I have developed a robust translational laboratory research program focused upon (1) elucidation of ‘miswired’ signaling networks within high-risk pediatric leukemia cells and learning how to disrupt their hyperactive communication using targeted inhibitor drugs and (2) preclinical testing of innovative ‘killer T cell’ therapies that harness the body’s immune system to attack cancer cells that have proven resistant to usual chemotherapy drugs. My laboratory is fortunate to have access to numerous primary patient samples for our research studies, which has allowed us to create a large cadre of sophisticated mouse models of high-risk childhood leukemias in which to test new treatments. As a clinician focused on precision medicine for children with blood cancers, I also have a keen interest in bench-to-bedside translation. Results from my laboratory have directly led to several clinical trials testing new inhibitor drugs or immune system therapies in children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In addition to my bench-based laboratory program, I am also an experienced clinical trialist and hold several leadership roles through the Children’s Oncology Group and the LLS Children’s Initiative PedAL consortium that oversee international portfolios of phase 1, 2, and 3 clinical trials. Personally leading early-phase leukemia trials of targeted inhibitor drugs or immunotherapies has provided invaluable perspective and new opportunities for bedside-back-to-bench investigation in which my laboratory studies blood and marrow samples from children treated on these trials to learn how the new drugs work and which patients may best respond to them. Ultimately, I hope that my ‘bilingual’ approach to childhood leukemia investigation with one foot firmly in the laboratory and one foot firmly in the clinic will engender more rapid development of biologically-rational precision medicine treatments for children with high-risk leukemias.

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