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Non-genotoxic combination treatments for paediatric acute leukaemias

Current treatments for childhood leukaemia achieve outstanding cure rates, but employ genotoxic compounds that can damage the genome of normal tissues. These treatments cause severe side effects during treatment and can also have substantial late effects such as reduced bone density, heart damage, fertility loss or development of new cancer. Novel, less genotoxic medicines are currently being explored but, when these drugs are used alone, the tumours often develop resistance, which leads to treatment failure.

Project Details

  • Project Title

    Non-genotoxic combination treatments for paediatric acute leukaemias

  • Lead Researcher

    Professor Olaf Heidenreich

  • Research Centre

    Newcastle University

  • City & Institution Postcode

    Newcastle

  • Start Date

    4 July 2017

  • Duration

    36 months

  • Grant Amount

    £237,514

Overview

In a collaboration involving research teams from Newcastle, Birmingham and Manchester, we identified therapeutic “Achilles heels” for a subtype of childhood leukaemia. Notably, a medicine named Palbociclib was recently introduced for treating breast cancer, which we found to exploit one of these “Achilles heels” of leukaemia.

Importantly, this medicine inhibits the growth of leukaemia, but does not damage the patient’s genome and is, thus, unlikely to have severe long-term consequences. In the next step, we need to combine this medicine with other medicines in order to enhance its efficacy and prevent the return of leukaemia.

Potential impact

The most important components of current treatment protocols for childhood leukaemia are genotoxic and may lead to undesired, life-threatening long-term effects. Developing novel non-genotoxic medicine cocktails will limit the long-term toxicity and the danger of treatment resistance. We expect such combinations to improve the cure rates for leukaemias and enhance the long-term quality of life of children with leukaemia.

About the research team

The research team is located in the Wolfson Childhood Cancer Research Centre at Newcastle University, a £5.5m facility opened in September 2016. It brings together over 90 scientists and clinicians working on childhood cancer in state-of-the-art facilities and is one of the few national and international units providing a complete research pipeline for childhood cancer, ranging from identifying treatment targets to developing new medicines and testing them in clinical trials.

The research team lead by Profs Olaf Heidenreich and Josef Vormoor are internationally recognized for their contributions to the treatment of childhood leukaemia including the development of models for pre-clinical medicine testing, the investigation of mechanisms of leukaemia propagation and the translation of research findings into clinical trials. This combined expertise will be crucial for succeeding in our quest for less toxic treatments of childhood leukaemia.

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