Funded by the Dick Vitale Gala
Acute lymphoblastic leukemia (ALL) is an aggressive cancer of the blood and a leading cause of disease-related death in children and adolescents. Cure rates of ALL have improved over the last decade thanks to innovative therapies, but it came at the cost of often severe toxicity associated with chemotherapy that can have long-lasting debilitating effects on children. The goal of our research is to move from the “sledgehammer” delivery of chemotherapy to “surgical precision” personalized ALL therapy, to minimize side effects and improve survival. We have recently discovered genetic factors (variations of our genetic make-up, DNA) that strongly influence the way thiopurine (an important anti-leukemic drug) is processed in patients, and we found that 80% of severe toxicity of this drug is due to genetic defects in two genes. Therefore, we reason that 1) patients should be tested for these DNA variations before ALL therapy starts, and 2) the genetic test results can be used to tailor chemotherapy for each patient to avoid toxicity, an approach also known as pharmacogenetics-based precision medicine. To achieve this goal, we have assembled an outstanding group of basic scientists and clinicians in 5 countries with diverse expertise, to preform comprehensive research in laboratory as well as clinical research in clinical trials of ALL. If funded, this work is likely to have immediate impact in the way we treat children and adults with ALL, demonstrating the importance genetics-guided precision medicine in cancer in general.