Cancer occurs through the uncontrolled division of cells. The number of times a cell can divide is limited by the length of specialised DNA sequences found at the end of chromosomes called telomeres. For a cell to become cancerous it has to stop its telomeres from shortening.
To accomplish this, cancer cells either activate an enzyme (telomerase), or they copy telomeric sequences from the end of one DNA molecule to another (the alternative lengthening of telomeres (ALT) pathway).
Importantly, it is predicted that ALT positive cancers are more susceptible to different therapeutic treatments than other cancers but to date there are no ALT-targeted therapeutics. Recent research has provided important clues as to how telomere lengthening is activated in ALT cancers. We have shown that expression of a protein ATRX, which is inactivated in most ALT cancers1, suppresses telomere lengthening in ALT cells2. This project will involve developing genetic and small molecule screens with a view to a) determine the mechanism underpinning telomere maintenance in ALT cancer and b) developing new ways to target ALT cancer cells