Accelerating the delivery of personalised treatment to children with neuroblastoma using MRI

18 September 2014
Dr Yann Jamin, The Institute of Cancer Research, London

Effective and safe treatments for children with neuroblastoma are urgently required. Neuroblastoma is the second most common solid tumour in childhood, accounting for six per cent of all childhood cancers, just under 100 children a year in the UK.

Promising novel therapies are currently being evaluated in the clinic. However there is a crucial need to accelerate the evaluation process that take these promising drugs from the laboratory bench to the children’s bedside.

Yann is looking at ways of transferring techniques now routinely used in adult cancers to use in children through the use of MRI technology. He will also explore new ways of monitoring response to treatment and identifying treatment resistance in children with neuroblastoma.

Amount of grant: £400,247 | Date of award: May 2014

Overview

In early clinical studies in adult oncology, measuring biological characteristics (biomarkers) such as specific proteins level is now routine. It allows investigators to understand if drugs are hitting their target in the cancer cell, but also to identify which patients will benefit most from each drug.

Biomarkers have revolutionised drug development, improving the response rates in adult cancer from 4per cent to 50per cent. This has not yet happened in children’s cancer. Conventional biomarkers often require the measure of specific molecules in post treatment tumour biopsy samples. This is not feasible in children – most children entering this type of clinical trial are in a very precarious condition making a biopsy, pre- and post- treatment, simply too much for them - and non-invasive alternatives must be identified.

About magnetic resonance imaging MRI

Magnetic resonance imaging (MRI) is a safe and non-invasive way to scan the body anatomy and is routinely used to assess tumours in children. Advanced functional and molecular MRI scans form images of key aspects of the tumour physiology including blood supply, altered metabolism and tissue architecture.

These key aspects are controlled by the genetic abnormalities which cause neuroblastoma and can be altered with successful targeted therapy.

Dr Jamin believes that MRI can provide specific biomarkers which can help:

  • identify children with genetic, pathological or metabolic variants of neuroblastoma
  • predict response and resistance to novel targeted therapeutics
  • accelerate the delivery of personalised treatments for children with neuroblastoma.

The scans required to measure these biomarkers can be easily introduced into existing standard anatomical MRI scans used in the paediatric clinic. However before being used in clinical trials, we need to ensure that the MRI biomarkers reflect the changes in tumour physiology that occur during therapy.

Dr Jamin’s research will incorporate advanced molecular and functional MRI scans in preclinical trials of novel targeted therapies using genetically-engineered models of high-risk neuroblastoma. These models replicate children’s neuroblastoma more accurately than any other models. As a result, the MRI-driven preclinical trials will provide a strong platform to identify and evaluate these MRI biomarkers.

Neuroblastoma Achilles heel

Key genetic abnormalities in high-risk neuroblastoma such as MYCN (the more established marker of poor prognosis in children with neuroblastoma), the physiological processes it controls and on which tumours depend to survive (including the growth of blood vessel and metabolism), represent neuroblastoma Achilles heel. These factors are currently being exploited as targets for more successful therapies.

Dr Jamin will first concentrate on demonstrating that functional MRI biomarkers of the vascular system and metabolism can predict/or assess the efficacy of novel drugs targeting the vascular system, metabolism, and MYCN protein. This approach will be extended to other models, used to emulate additional key genetic abnormalities such as the anaplastic lymphoma kinase (ALK) gene, which is associated with marked poorer prognosis for children with high-risk neuroblastoma but also represent a promising target for therapy.

About the research team

Dr Yann JaminDr Jamin has ten years of experience in developing and implementing MRI methodologies and in evaluating and validating MRI biomarkers in cancer models in the Preclinical Imaging Team led by Dr Simon Robinson within the Cancer Research UK Centre for Cancer Imaging, at The Institute of Cancer Research, London.

In this programme of research Dr Jamin will work closely with Dr Louis Chesler, who aims to develop novel MYCN-targeted therapeutic strategies for high-risk neuroblastoma and the ICR and Royal Marsden Paediatric Drug Development Unit, led by Professor Andrew Pearson. He will also work in close collaboration with the pioneers of state-of-the-art MRI methodologies that he aims to introduce in the paediatric clinic, including Dr Simon Walker-Samuel from University College London, Dr James O’Connor from the University of Manchester and Professor Ralph Sinkus from King’s College London.

“Five years ago, through collaborations with Dr Louis Chesler and Professor Andy Pearson, who are both world-leading experts in neuroblastoma, I was introduced to the fascinating biology of neuroblastoma but also the sad clinical reality for children with this disease. This is when I decided to dedicate my research to children with cancer. This is exactly what the Paul O’Gorman post-doctoral research fellowship will enable me to do”
Dr Yann Jamin

What difference will this research make?

Through this research programme, Dr Jamin aims to demonstrate that advanced magnetic resonance imaging (MRI) scans can identify the most aggressive forms of neuroblastoma as well as predicting or monitoring the response to novel treatments, and guide their introduction in clinical trials for children with neuroblastoma.

There is an urgent need to accelerate the delivery of novel promising tumour-targeted therapies from the laboratory bench to the children’s bedside.

This research will facilitate the introduction of both novel therapies and associated MRI biomarkers in early phase paediatric clinical trials.

Overall, functional MRI biomarkers will accelerate the delivery of precision medicine to children with neuroblastoma, while reducing the need for invasive procedures, ultimately improving survival while decreasing the burden for children during treatment.

Finally, although the focus of the research programme is on neuroblastoma, the functional imaging biomarkers and methods will generally be applicable to most childhood solid tumours including brain tumours and rhabdomyosarcomas.

Read more: About neuroblastoma | Other neuroblastoma research | Patient stories
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