Targeting the anti-apoptotic BCL-2 dependence in Multiple Myeloma
Dr Tríona Ní Chonghaile and Lyndsey Flanagan
Lyndsey Flanagan has been awarded the Breakthrough cancer Research Scholarship 2020. Lyndsey will work with Lyndsey will work with Dr Tríona Ní Chonghaile and Dr. Siobhan Glavey in the Royal College of Surgeons in Ireland.
Multiple Myeloma (MM) is a cancer of the antibody producing cells in our body, called plasma cells. These cells grow uncontrollably in the bone marrow and this leads to a variety of symptoms including tiredness, bone pain and increased infections. While there have been great improvements in the treatment of MM, unfortunately it remains incurable. BCL-2 is a protein that controls the survival of human MM cells. One way that cancer cells can become resistant to treatment is through increased reliance on BCL-2. Recently, a BCL-2 inhibitor called ABT-199 was developed, and it selectively targets cells that are reliant on BCL-2. Our aim is to identify MM cell lines and patient samples that are reliant on BCL-2 for survival and we will do this using a technology called BH3 profiling. We will screen a panel of epigenetic modifier drugs, which are drugs that can turn genes on and off, and see if they can make MM cells more reliant on BCL-2. In this way, the MM cells will be more sensitive to ABT-199 treatment. Additionally, there is a need for a biomarker, or a tool, that can be used to accurately identify BCL-2 dependence in MM cell lines and patient samples.
The aim of this project is to use the BH3 profiling technology to identify MM patient samples that are reliant on BCL-2 for survival and will be sensitive to ABT-199 treatment. Our hope is that this new combination of drugs will work to ensure a longer treatment response in MM patients.
Publications
Lyndsey Flanagan, Siobhan Glavey, Triona Ní Chonghaile. Functional Precision Profiling: The Way Forward for Personalized Medicine. Commentary – Journal of Clinical Haematology (2021) Volume 2, Issue 3
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