Prof Andreas Strasser, Dr Daniel Gray
The Walter and Eliza Hall Institute of Medical Research
Cell competition is the process whereby fit cells are favoured over weak or harmful cells to maintain tissue integrity. Competition between cells has become an emerging principle in cancer biology and has major implications on the initiation, progression and treatment of malignant disease. Recent findings have suggested that cell competition acts as a tumour suppression mechanism in acute T lymphoblastic leukaemia in humans, however the molecular mechanism that underpins this activity is unknown.
We propose to test that the induction of cell death (apoptosis) in unfit, pre-malignant cells is vital to suppress the development of cancer. We will test this concept in a new model of acute T lymphoblastic leukaemia.
What is the need?
Current treatments for many cancers are not effective and it is becoming clear that cancers can adapt to various treatments to cause relaps. Understanding the molecular mechanisms of cell competition will provide the basis for creating new therapies and using existing treatments more effectively.
Our project will provide knowledge directly relevant to the initiation, maintenance and relaps of malignant disease in cancer patients. It may also offer new therapeutic indications for the new generation of drugs that directly target the apoptotic machinery in cancer cells.
What impact will this research have?
We are performing this research using advanced, innovative models of acute lymphoblastic T cell leukaemia so our data will help show how blood cancers arise. We expect to identify markers of disease progression that are directly related to cell competition.
Furthermore, our focus on cell death and survival mechanisms creates the opportunity for translation into clinical practice. We hope to improve the tool-kit that clinicians have for the deterction, monitoring and treatment of malignancies by revealing the mechanisms they rely upon to out-complete healthy cells.
Study the changes in the cell death/ survival pathways that accompany cell competition.
Test the involvement of key molecules in cell death/survival pathways, to see which is important in preventing cancer.
Leverage some of our insights by restoring fitness to cells that would otherwise be unable to compete with normal cells.
|Confirm the results from the cohort studies by overexpressing the molecules in unfit cells to see whether this could induce cancer.
"We hope to improve the tool-kit that clinicians have for the detection, monitoring and treatment of malignancies by revealing the mechanisms they rely upon to our-compete health cells."