Targeting PI3Kdelta in Childhood Acute Lymphoblastic Leukemia
The Samantha Hill Childhood Cancer Hero Reach Grant
Although many children who are treated for acute lymphoblastic leukemia (ALL) are cured, a significant percentage are not, and when this happens the prognosis is grim. Therefore, we need new ideas for treatment of relapsed ALL. Instead of targeting only the leukemia cells, we look at a wider target: the leukemia cells as well as the protective non-leukemia cells, which are located in the bone marrow and create a safe haven for ALL cells.
When leukemia cells attach to bone marrow cells, a protein called PI3Kd triggers pro-survival signals inside the leukemia cell. Using an inhibitor of PI3Kd, we showed that this drug kills ALL cells and, importantly, makes them more sensitive to chemotherapy. We also developed a clinically useful method to track PI3Kd activation.
We propose preclinical studies to determine how PI3Kd inhibition could be used to optimally treat relapsed ALL. We aim to:
- Find if there are certain subtypes of ALL that would benefit more than others from this treatment
- Find how it kills ALL cells
- Refine a test to monitor drug treatment in clinical trials.
Positive results of this evaluation of PI3Kd inhibition in ALL will be followed by a clinical trial in patients with ALL, done in conjunction with a clinical trial consortium, TACL, headquartered at Children's Hospital Los Angeles.