Apo2L/TRAIL as a regulator of cell death in transformed cells
Apoptosis, also known as programmed cell death or ‘cell suicide’, is a normal biological process that enables old or unhealthy cells to be ‘killed’. Cancer cells do not undergo this process enabling them to continuing multiplying unchecked. We are interested in the protein TRAIL or TNF-related apoptosis-inducing ligand, which is a key apoptosis regulator. Our research has found that PTHrP expression by breast cancers modulates tumour response to TRAIL. We aim to identify the mechanism by which PTHrP confers enhanced TRAIL sensitivity.
Disturbances in mechanisms that direct abnormal cells to undergo cell death frequently and critically contribute to tumourigenesis, yielding a logical target for potential therapeutic intervention.
There is currently heightened interest in the extrinsic apoptosis pathway, with several pro-apoptotic receptor agonists (PARAs) in development. One of these PARAs includes the recombinant ligand Apo2L/TRAIL.
TRAIL or TNF-related apoptosis-inducing ligand is a key regulator of cell-death. Gene array studies comparing cancer cells that respond to Apo2L/TRAIL compared to those that do not respond have identified several genes that may be involved in determining cell fate.
We are continuing to examine the role of these genes with a particular emphasis on overcoming Apo2L/TRAIL resistance. Notably, PTHrP expression by breast cancers alters their response to TRAIL as well as several target genes within the TRAIL pathway.