Children who develop ‘high risk’ acute lymphoblastic leukaemia, subtypes that grow aggressively and are often resistant to standard treatments, often relapse and many of these children die from their disease.
One common type of high-risk acute lymphoblastic leukaemia for which new therapies are urgently needed is ‘Philadelphia chromosome-like ALL’ (Ph-like ALL), named for its similarity to another type, Ph-positive ALL.
“New therapies are urgently needed for high-risk acute lymphoblastic leukaemia,” said lead researcher Richard Lock, Professor, Head of the Blood Cancers Theme at Children’s Cancer Institute.
“We are very encouraged by our results, which suggest we could be on the way to developing a more effective way to treat this cancer in some children,” Lock added.
For the study, published in the journal Leukemia, the team tested more than 5,000 drugs in combination with the kinase inhibitor, ruxolitinib.
They found that ruxolitinib worked synergistically with several types of commonly used anticancer drugs, the most effective being glucocorticoids, topoisomerase I and II inhibitors, microtubule targeting agents and antimetabolites.
Based on their in vitro findings, the researchers then carried out in vivo testing in living models of a disease known as ‘patient-derived xenograft models’ (PDXs) or ‘avatars’: mice specially bred to grow leukaemia cells taken from individual patients with CRLF2r Ph-like ALL.
The results showed that the addition of ruxolitinib to a common treatment regimen called VXL (consisting of vincristine, 2dexamethasone and L-asparaginase) enhanced treatment efficacy in two out of three avatars, achieving long-term suppression of leukaemia growth in one of these.
“The enhanced effect of treatment when ruxolitinib was added and the variety of drug classes found to synergize with ruxolitinib in our laboratory, suggest promising potential for kinase inhibitors in the treatment of Ph-like ALL,” said Lock.