In the last few decades, acute lymphoblastic leukemia (ALL) has become a cancer success story with over 80 per cent survival among children. This has been achieved mostly through intensive chemotherapy, which that has improved outcomes for many, but unfortunately not for all. Still about 20 per cent of children with ALL will relapse, and survival among adults is just 40 per cent.
A novel study led by The Hospital for Sick Children (SickKids) opens the door to a potential new treatment for ALL in both children and adults. The study, published in the May 14 online edition of Science Translational Medicine, not only identified a molecular pathway needed for leukemic cell growth, but also found and tested a promising drug for treating poor-prognosis and relapsed ALL.
“Until now, there has not been a rationale for using targeted treatments for the majority of patients with ALL. We have continued to use drugs that were established decades ago. Our findings demonstrate a treatment that targets a communication pathway that is abnormally active in many ALL cases, and could eventually lead to less intensive chemotherapy which could reduce late effects of toxic cancer therapies among children and adults,” says Dr. Jayne Danska, Senior Scientist in Genetics & Genome Biology at SickKids.
Danska and her collaborators demonstrated in a mouse model that this pathway, called the spleen tyrosine kinase or SYK pathway, is driving the growth, spread and survival of leukemic cells in the body. They then looked at 80 diagnostic leukemic cell samples from paediatric and adult patients to see if this pathway was in fact activated, and found that it was.
There are existing drugs that target and inhibit the SYK pathway. The research team tested two of these for the effect against ALL cell growth in laboratory cell culture and after transplanting the patient ALL cells into mice. In both scenarios, the SYK inhibitor successfully stopped growth and spread of human leukemia in the transplanted mice, including in the brain, which is common and dangerous site of ALL spread.
With such promising results, the next step is to bring this treatment to clinical trials. “Another important advance we have made is that we could take cells from each patient before a clinical trial to first see if the SYK pathway is activated, whether the inhibitor blocks growth of the patient’s cells in laboratory culture before deciding to test the drug in the patient.” said Dr. Danska.
This work was supported by the Cancer Stem Cell Consortium (CSCC) with funds through Canadian Institutes for Health Research (CIHR), Genome Canada (through the Ontario Genomics Institute), the Ontario Institute of Cancer Research and SickKids Foundation.