New research paves the way for safer leukemia treatments

An international team of researchers has discovered a new and much safer way to treat a type of leukaemia that mainly affects children: T-cell acute lymphoblastic leukemia (T-ALL).

Published this week in Science Translational Medicine, the research is a joint effort of Children’s Cancer Institute (Australia), VIB-KU Leuven (Belgium) and UK Dementia Research Institute (England), and is an important breakthrough in the effort to find safer ways to treat T-ALL

“Children with T-ALL are at high-risk of a poor outcome and so are given very intensive chemotherapy,’ said Dr Charles de Bock, Team Leader at Children’s Cancer Institute. ‘Many of these children suffer long-term effects of this aggressive treatment. There is therefore a great need for new therapies that can minimise these effects.”

The breakthrough involves drugs called gamma-secretase inhibitors, which work by inhibiting the action of the enzyme ‘gamma-secretase’, an important driver in many cases of T-ALL. Previously, gamma-secretase inhibitors were found to be unsuitable as a treatment for children because of their toxicity. However, this latest research appears to have found a way around the problem.

In an interesting twist, Alzheimer’s disease researchers have been studying the same enzyme, as it is known to be involved in the processing of amyloid-beta which is strongly linked to neurodegeneration. Professor Bart De Strooper, VIB-KU Leuven Center for Brain & Disease Research and UK Dementia Research Institute, and a collaborator on the T-ALL research, explains: “Gamma-secretase is a complex that exists in very different versions. Clinical trials have been performed using non-selective inhibitors that target all versions of the complex equally. We wanted to explore whether inhibiting specific versions could fine-tune the treatment and reduce side-effects.”

Dr de Bock and fellow cancer researcher, Dr Roger Habets, VIB-KU Leuven, looked closely at gamma-secretase in cells, finding that the relative abundance of different versions of the complex was strikingly different in leukemia cells compared with healthy cells. This led to a range of laboratory experiments which showed that targeting just one version of the complex stopped T-ALL from growing, without causing the toxicity previously associated with this class of drugs.

Dr de Bock is optimistic about the rapid translation of this research into the clinic. “Historically, these types of drugs have had very limited success due to their toxicity. Now, for the first time, we have provided proof that selectively targeting a specific version of the gamma-secretase complex is both effective and safe.”

“In the future, it may even prove possible to use this approach for other types of cancer, and potentially some other diseases” he added.

Originally trained in Australia, de Bock spent several years at VIB-KU Leuven Center for Cancer Biology before joining Children’s Cancer Institute in January 2019 to establish his own research team. In his new role, he hopes to significantly improve understanding of how T-ALL develops, as well as continue working on new therapies.

“I’m passionate about seeing our research translate into better outcomes for people with cancer,” said de Bock. “There’s not a day in the lab that I don’t feel excited about what we are going to find out next.”

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Habets et al (2019). Safe targeting of T-cell acute lymphoblastic leukemia by pathology-specific NOTCH inhibition.
Science Translational Medicine

Media Contact:

Children’s Cancer Institute:

Ashleigh Addison

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Phone: 0418 274 428

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. Forty 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

About VIB

Basic research in life sciences is VIB’s raison d’être. VIB is an independent research institute where some 1,500 top scientists from Belgium and abroad conduct pioneering basic research. As such, they are pushing the boundaries of what we know about molecular mechanisms and how they rule living organisms such as human beings, animals, plants and microorganisms. Based on a close partnership with five Flemish universities – Ghent University, KU Leuven, University of Antwerp, Vrije Universiteit Brussel and Hasselt University – and supported by a solid funding program, VIB unites the expertise of all its collaborators and research groups in a single institute. VIB’s technology transfer activities translate research results into concrete benefits for society such as new diagnostics and therapies and agricultural innovations. These applications are often developed by young start-ups from VIB or through collaborations with other companies. This also leads to additional employment and bridges the gap between scientific research and entrepreneurship. VIB also engages actively in the public debate on biotechnology by developing and disseminating a wide range of science-based information. More info can be found on http://www.vib.be