A/Prof Mark Shackleton, A/Prof Kieran Harvey
Peter MacCallum Cancer Centre, The University of Melbourne
Our research is focused on a specific group of proteins, collectively called the Hippo family proteins, which are important in the growth of some cancers. We are specifically focused on how Hippo proteins promote a type of skin cancer called melanoma, which might grow when one of the key Hippo proteins, called YAP, is abnormally active.
So far, we have found that YAP is overactive and drives melanomas, suggesting that YAP may be inhibited with drugs to prevent the onset of cance. We have also discovered one of the first described genetic mutations affecting YAP in a patient with melanoma.
Our ultimate aim is to help develop anti-cancer drugs that target YAP and other Hippo proteins.
What is the need?
There is a major need for new cancer treatments, as the outcomes of current treatments are too often not good enough. We are studying Hippo family proteins, which were discovered by members of our team just over a decade ago, because they might be good targets for new cancer drugs. This possibility is based on observations that cancers form, grow and spread when Hippo proteins become too active - particularly YAP>
What impact will this research have?
This discovery of anti-YAP drugs is a major focus of numerous academic and pharmaceutical endeavours at the moment - once these drugs are discovered, it will be important to test them in patients as soon as possible. A key to this will be identifying which patients are likely to respond to these drugs, and our research will inform that.
In contributing to the development and application of a new class of anti-cancer drugs (e.g. YAP inhibitors), our research will define potential roles for these drugs in patients and those at risk of melanoma. This might also have implications for people affected by other cancers in which the YAP protein is overactive.
For the first time, we identified a novel genetic mutation affecting the YAP gene that causes it to become overactive, and potential biomarkers.
Identified that YAP is overexpressed in melanomas as they progress and spread.
Understanding how YAP regulates the growth of melanomas as distinct from their ability to spread.
Understanding the signals that YAP activates to promote melanoma growth and spread, which may lead to the discovery of new drugs.
"Our ultimate aim is to help develop anti-cancer drugs that target YAP and other Hippo proteins."