Overview
In multicellular organisms fatal cancers occur when mutated cells proliferate and survive inappropriately. The human body is composed of approximately 1014 cells, which fall into a multitude of diverse cell types. Given the vast number of cells in our body it is rather surprising how little generally goes wrong. One of the reasons is the body’s astounding ability to correct for errors.
Each cell carries within it a built-in ‘auto-destruct mechanism,’ which limits the survival and expansion of a cell if it becomes potentially harmful or malignant. Thus, cancer cells that spontaneously arise out of these 1014 cells are normally eliminated because the cell activates its intrinsic suicide programme. This self-destruct mechanism – called ‘apoptosis’ – is a key defence strategy against the emergence of cancer.
The significance of apoptosis in cancer surveillance is illustrated by the fact that growth-deregulating lesions not only promote cell proliferation but also trigger apoptosis. Consistently, cancer cells are often characterized by increased resistance to apoptosis allowing their survival under abnormal growth stimulation. Moreover, alterations in the apoptotic machinery or its regulatory components appear to be a major cause for resistance to apoptosis induced by anticancer drugs.
Our Focus
We are attempting to resolve how cancer cells bypass apoptosis and survive and propagate inappropriately. To this end, we are focusing on the machinery that executes apoptosis, and the molecular mechanisms that control this potentially catastrophic process. Our work concentrates on members of the Inhibitor of Apoptosis (IAP) protein family, which act as potent inhibitors of caspases, a group of highly specialised proteases that execute the cell death programme. A better understanding of the process that controls apoptosis will provide a rational basis for the development of novel therapeutic strategies aimed at selectively killing cancer cells.
