New drug combo found effective against high-risk leukaemia
New drug combination found to be effective against high-risk leukaemia
2021-05-28
(Press-News.org) Australian scientists have found what could prove to be a new and effective way to treat a particularly aggressive blood cancer in children.
Acute lymphoblastic leukaemia, or ALL, is the most common cancer diagnosed in children. Despite dramatic improvements in the survival of children with ALL over past several decades, children who develop 'high risk' ALL - 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 ALL 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. Shared genetic characteristics of these two types of high-risk ALL have led scientists to hypothesise that they
may respond to similar treatments; specifically, a newer class of drugs known as kinase inhibitors.
However, experiments have shown that cases of Ph-like ALL that contain a genetic mutation known as CRLF2r - about half of all cases of this subtype - respond poorly to kinase inhibitors when used as a single agent. Scientists have since been investigating whether kinase inhibitors are more effective when used in combination with other agents.
In new research published this week in the international journal Leukemia, scientists at Children's Cancer Institute tested more than 5000 drugs in combination with the kinase inhibitor, ruxolitinib, finding 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.
"New therapies are urgently needed for high-risk ALL," said lead researcher Professor Richard Lock, 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."
Based on their in vitro findings, the researchers then carried out in vivo testing in living models of 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. 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 Professor Lock. "We hope this leads to improved treatment options for children with this leukaemia in the near future."
INFORMATION:
About Children's Cancer Institute
Originally founded by two fathers of children with cancer in 1976, Children's Cancer Institute is the only independent medical research institute in Australia wholly dedicated to research into the causes, prevention and cure of childhood cancer. More than 40 years on, our vision remains unchanged - to save the lives of all children with cancer and to eliminate their suffering. The Institute has grown to now employ nearly 300 researchers, operational staff and students, and has established a national and international reputation for scientific excellence. Our focus is on translational research, and we have an integrated team of laboratory researchers and clinician scientists who work together in partnership to
discover new treatments which can be progressed from the lab bench to the beds of children on wards in our hospitals as quickly as possible. These new treatments are specifically targeting childhood cancers, so we can develop safer and more effective drugs and drug combinations that will minimize side-effects and ultimately give children with cancer the best chance of a cure with the highest possible quality of life.
More at http://www.ccia.org.au
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[Press-News.org] New drug combo found effective against high-risk leukaemia
New drug combination found to be effective against high-risk leukaemia
