Use of Targeted Cancer Therapies to Treat High-risk Subtypes of Pediatric Acute Lymphoblastic Leukemia (ALL)

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) and early T-cell precursor ALL (ETP-ALL) are high-risk subtypes of ALL that are characterized by aggressive disease progression and poor prognosis.

Using mouse xenograft models of ALL, researchers at the Center for Childhood Cancer Research, including David T. Teachey, MD, and Shannon L. Maude, MD, PhD, found that both Ph-like ALL and ETP-ALL have dysregulated cell signaling in MAPK, JAK/STAT and PI3K/AKT/mTOR pathways.

Additional studies revealed that a Jak inhibitor called ruxolitinib was highly active in slowing disease progression in both Ph-like-ALL and ETP-ALL disease models. Ruxolitinib is a targeted cancer therapy that has previously been approved to treat adult myeloproliferative diseases.

Early stage clinical trials in partnership with the Children’s Oncology Group (COG) are being developed to evaluate the efficacy and safety of a combination of ruxolitinib with standard chemotherapy to treat high-risk ALL with dysregulated Jak/STAT signaling mutations.

Other studies are currently underway to identify novel targeted cancer therapies that can be used to safely and effectively treat high-risk subsets of pediatric ALL.