Ms Margs Brennan
Researcher: Margs Brennan
and Eliza Hall Institute of Medical
Project title: Testing a new anti-cancer drug for the treatment
Disease focus: Lymphoma
Annual Funding: $40,000
Funding period: 2015-2017
Margs Brennan is assessing a potential new anti-cancer drug that selectively targets and inhibits a protein called MCL-1 (myeloid cell leukaemia 1).
A research team at the Walter and Eliza Hall Institute of Medical Research (WEHI) led by Margs’ PhD supervisors, Dr Marco Herold, Professor Andreas Strasser and Dr Gemma Kelly, recently identified MCL-1 as a therapeutic target for lymphomas and leukaemias.
The team found MCL-1 was the key survival protein that sustains MYC-driven lymphomas, such as Burkitt lymphoma and diffuse large B-cell lymphoma. MYC is a potent gene that can transform a cell into a tumour cell. In preclinical laboratory tests, disabling the MCL-1 protein led to the rapid death of lymphoma cells.
Following this breakthrough discovery, the team accessed a potential new MCL-1 inhibitory drug candidate. Using unique lymphoma/leukaemia laboratory models developed at WEHI, Margs now is testing the effectiveness of this compound in killing lymphoma cells. Positive outcomes from her research will significantly increase the chances of an MCL-1 antagonist entering the clinic.
“We’re extremely excited and optimistic about the potential of this new MCL-1 inhibitor to vastly improve the treatment strategies for lymphoma and leukaemia,” Margs said.
“It means a great deal to me to contribute to the improvement in lymphoma and leukaemia treatment and help relieve some of the stress experienced by families, as well as to reduce the burden on the healthcare system caused by these often devastating cancers.”
MCL-1 is one of several proteins involved in regulating a process called programmed cell death (apoptosis). The body uses this process to maintain the number of healthy and functioning cells in our tissues. (When cells are no longer needed or become damaged, they commit suicide.) However, inherent defects in tumours often impair the apoptosis pathway and often this is critical for the continued expansion of such cancers.
The Leukaemia Foundation also awarded a 2015 Postdoctoral Fellowship to WEHI’s Dr Stephanie Grabow to investigate the function of MCL-1 in normal blood cells and the development of leukaemia and lymphoma.
The breakthrough WEHI research into MCL-1 was partly funded by the Leukaemia Foundation (see Genes & Development).