20 years of research offers hope for rare cancer

Publicly released:
Australia; VIC

Researchers at Peter Mac are using their knowledge of an ancient signalling pathway to find new treatments for mesothelioma, a devasting cancer that has few effective treatments and a very poor prognosis.

Media release

From: Peter MacCallum Cancer Centre

Researchers at Peter Mac are using their knowledge of an ancient signalling pathway to find new treatments for mesothelioma, a devasting cancer that has few effective treatments and a very poor prognosis

Dr Kieran Harvey, Group Leader and Program Head at Peter Mac, helped discover the ‘Hippo’ signalling pathway 20 years ago and has spent his career trying to understand more about how this pathway controls organ growth and how we can target it to treat cancer.

There are currently five treatments being tested in early clinical trials that target the Hippo pathway and most of these are being trialled as mesothelioma treatments, because the Hippo pathway is the driving force behind this particular cancer.

Dr Harvey said that it was incredibly rewarding to see his discoveries lead to potential clinical treatments that were being tested at Peter Mac in patients with mesothelioma.

“These new treatments work by inhibiting TEAD, a type of protein that helps control organ growth, however people will likely develop resistance to the treatment so we have been researching ways to stop this from occurring,” he said.

“In our study published earlier this month in EMBO Reports we conducted genome wide screens in mesothelioma cells and uncovered that the RAS pathway causes resistance to TEAD inhibition. What’s exciting is that we already have treatments available that target this pathway.

“In this study we combined the two treatments and found that they worked synergistically to block proliferation of multiple mesothelioma and lung cancer cell lines and tumours.”

Dr Harvey explained that the next step is to test this treatment combination of a TEAD inhibitor coupled with a RAS pathway inhibitor in people with mesothelioma to verify it works in the real-life setting.

“Peter Mac is in a unique position to be able to undertake informative lab research and apply this knowledge to develop more effective treatments to be tested in clinical trials,” he said.

“Peter Mac has been involved in the first two clinical trials of TEAD inhibitors and we hope to apply this knowledge to test a new combination treatment strategy to help people with mesothelioma live longer.”

This study was a collaboration between the Harvey lab, Vivace Therapeutics, USA and researchers at Peter Mac, Monash University and the University of Melbourne.

Mesothelioma is an asbestos driven cancer with approximately 900 Australians diagnosed each year.

Journal/
conference:
EMBO
Research:Paper
Organisation/s: Peter MacCallum Cancer Centre
Funder: KFH was supported by a Senior Research Fellowship (APP1078220) and Investigator grant (APP1194467) from the National Health and Medical Research Council of Australia (NHMRC). AK was partly supported by an Australian Government Research Training Program Scholarship and Rosie Lew Peter MacCallum Cancer Foundation Postgraduate Award. This research was supported by a Lyall Watts Mesothelioma Research Grant from the Cancer Council Victoria (APP1157737) and the Peter MacCallum Cancer Foundation.
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