Establishing new ways to eliminate childhood neuroblastoma

01 March 2013

Dr Karim Malik, University of Bristol

Neuroblastoma is one of the most common childhood cancers and more than a third of patients do not survive. A major problem with treatment is that neuroblastomas that are initially responsive to treatment often relapse. Dr Malik is working to understand more about the mechanisms of neuroblastoma growth and development in order to open up new approaches to treatment.

Amount of grant: £143,702  |  Date of award:  March 2013

Overview

Although the treatment of many childhood cancers has improved dramatically, certain cancers, including neuroblastoma, still have a poor prognosis.

Neuroblastoma is one of the most common solid tumours of childhood and, despite some recent improvements in therapy, more than a third of patients do not survive longer than five years from diagnosis. Furthermore, neuroblastomas that are initially responsive to therapy often relapse.

Opportunities for the development of improved treatments for neuroblastoma are limited by our understanding of the mechanisms by which neuroblastoma arises, how the growth of the cancer cells is maintained, and how, even after intensive treatment, the cancer can return.

Dr Malik’s work focuses on one of the main biological methods for regulating the growth of cells, the so-called Wnt pathway. This pathway relies on cells sending each other signals to increase each other’s growth or proliferation. One cell will secrete a protein (ligand) that the recipient cell will recognise by means of another protein on its cell surface (receptor). In normal cells, the production of ligands and receptors is carefully regulated but in cancer cells they may be over-produced, resulting in uncontrolled proliferation. Excessive Wnt pathway activity, leading to excessive cell growth, is a causative mechanism in many cancers.

Dr Malik and colleagues have found that highly malignant neuroblastoma cells produce high levels of a Wnt pathway receptor. They believe that this gives neuroblastoma cells the ability to proliferate without restraint and also to survive current anti-cancer therapies.

Targeting these proteins offers the opportunity for therapeutic intervention and in this study Dr Malik and colleagues will analyse the function in relation to neuroblastoma growth and explore new approaches to treatment.

About the research team

Dr Malik and his colleagues in Bristol have a long history of research into childhood cancers and have published widely on cancers including neuroblastoma. Excellent collaborations within the University of Bristol add supportive technical expertise in key areas.

What difference will this project make?

This work will provide important new insights into the mechanisms underpinning growth and survival of neuroblastoma tumour cells and ultimately should provide the basis for desperately-needed new therapies for children with poor prognosis neuroblastoma.

Read more: Neuroblastoma
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