Rosetrees researcher profile: Dr. Stuart Rushworth and Professor Kristian Bowles, Norwich Medical School, University of East Anglia
Who Rosetrees Trust is funding
Current treatment options for patients with acute myeloid leukaemia (AML), including curative cytotoxic chemotherapy, are limited by their intensity and side effects. They are most commonly used to treat younger, fitter patients, but this is a disease mainly of older people. Therefore, in addition to these existing treatment options, patients that are older and less fit would require alternative therapy options that can be better-tolerated. Even in younger patients treatments need to be improved to increase survival and reduce side effects.
Research by the Norwich team and others shows that there is a high dependence of AML on external signals from bone marrow stromal cells (BMSC) for its survival. So, tumour cell-to-cell interactions and the microenvironment represent a potential target for novel treatment strategies.
Previously, Dr. Stuart Rushworth and Professor Kristian Bowles and the team at Norwich Medical School have investigated how AML survives the cellular challenges of its rapid growth and chemotherapy. With Rosetrees support the team further investigated what makes the bone marrow microenvironment, in which the leukaemia grows, so important in this process. The aim of the work is to ultimately exploit these interactions between the blood cancer and the cells that surround it, in order to identify a novel tumour-specific treatment strategy that can be used for all patients with AML patients.
How Rosetrees Trust have supported Dr. Stuart Rushworth and Professor Kristian Bowles
The team in Norwich received their first Rosetrees Trust grant in 2015. This project funded PhD student Chris Marlein who completed his degree in the Autumn of 2018.
What the outcomes are of Rosetrees Trust-funded research from Dr. Stuart Rushworth and Professor Kristian Bowles
The team, including Dr. Rushworth, Professor Bowles, and Chris Marlein, the PhD researcher on this project, have identified new key interactions between non-malignant cells of the bone marrow microenvironment and leukaemia cells. Furthermore, they discovered how these processes support the energy requirements of the cancer cells.
AML cells require large amounts of energy to grow and survive chemotherapy. It had not been fully understood how, and to what extent, the bone marrow microenvironment supports the energy requirements of the leukaemia cells. The team in Norwich have shown that functional mitochondria (energy generating organelles) are transferred, via nanotubes, from non-malignant stromal cells to the malignant cell. This process significantly enhances the growth capacity of the cancer cell, whilst at the same time providing chemoresistance. This output from this Rosetrees-funded work has been reported in a number of publications, including the following Cancer Research, Leukemia, Blood and Haematologica (Epub ahead of print).
Their research has major implications for this research field, including the identification of two proteins (NOX2 and CD38 – Epub ahead of print) as molecular targets which could act as therapeutic targets in the treatment of AML and other haematological malignancies. Overall, this work is hoped to lead to new drug development and clinical trials in the near future. For example, immediately the team provide the rationale for clinical trials of antibodies targeting CD38 in patients with AML (Epub ahead of print) and further explain how these drugs function in other blood cancers.
Rosetrees Trust support on this project has helped the team secure further funding from the Wellcome Trust, the MRC and the Big C, totalling almost £1 million. Furthermore, Dr. Rushworth has led expansion and development of the lab as a whole, and Dr. Chris Marlein has launched his academic career.
Written by: Dr. Rebecca Downing, Dr. Stuart Rushworth, and Professor Kristian Bowles
Further details at https://www.rushworthlab.com