One of its characteristics is the controlled disassembly of the cell into apoptotic bodies, which are eliminated. Since oncogenic stress signals are inducers of apoptosis, this cell death pathway must be suppressed in most forms of cancer. This is typically achieved by mutations that inactivate promoters of apoptosis, such as the tumor suppressor p53 and other guardians of DNA integrity. Alternatively, cell death is inhibited by dominant suppressors of apoptosis, such as the Bc1-2 family of death suppressors. Execution of the intrinsic cell apoptosis pathway involves critical transformations in the mitochondria and endoplasmic reticulum, which lead ultimately to the activation of a class of cysteine proteases, named capases, which are responsible for the demise of the cell.

The ability to re-activate the otherwise suppressed apoptosis machinery in cancer cells represents a therapeutic opportunity, and this opportunity is being examined, in order to discover ways to manipulate key regulators of the apoptotic pathways. A detailed understanding of apoptosis and uncovering its “Achilles heel” in various contexts could provide advances in the treatment of cancer. Our research programme will continue to focus on understanding the role of intracellular pathways and identify the key molecular players of apoptosis and other cell death pathways that may be of importance in cancer or virus infection.

The team:
Dr. Philip Branton
Dr. Imed Gallouzi
Dr. Gordon Shore
Dr. Maria Zannis-Hadjopoulos