Peter Mac research projects have received more than $17.6m in the latest grant round from the National Health and Medical Research Council (NHMRC).
This includes $4.8m for Prof Bernhard Riedel to lead an international trial to investigate if type of anaesthesia used during cancer surgery affects long-term patient outcomes.
Prof Michael Henderson will also test a new surgical protocol for removing melanoma ($2.7m), Prof David Bowtell will trace how ovarian cancers develop drug resistance ($1.1m) and Prof Sarah Jane Dawson will examine use of blood tests to actively monitor, and inform treatment, of lung cancer patients ($765K).
There are also new studies to investigate novel immunotherapy-based treatments, and basic research to better understand the fundamental drivers of cancer.
“These diverse projects speak to the broad pipeline of innovative research underway at Peter Mac which is focussed on understanding the molecular and biological drivers of cancer, advancing cancer treatment and improving patient outcomes,” says Peter Mac’s Executive Director of Cancer Research, Professor Ricky Johnstone.
“We are particularly excited to be able to start two large trials in cancer surgery as well as important hypothesis-driven and translational projects which help bridge the gap from basic discovery to new drugs.
“The NHMRC is to be thanked for enabling these projects to proceed, and for their support of the excellent clinical and laboratory research teams behind them.”
Two “New Investigator” grants were awarded to early-career researchers Dr Mohammad Haskali from Molecular Imaging, and Dr Marian Burr from Prof Mark Dawson’s lab.
In total, Peter Mac researchers were awarded 12 grants totalling $17,624,107. This is almost double the result of the previous year, when Peter Mac received 11 grants totalling $9.2 million.
Latest NHMRC Grant Outcomes
Prof Kieran Harvey (Sole CI - $707,372) Examination of Hippo signalling in real time, in vivo. Summary: A new frontier in biomedical research will involve watching individual proteins work in real time, in living organs. Here, we will investigate the Hippo signalling pathway, which is an important regulator of organ growth and is mutated in many human cancers. We will monitor the movement of different Hippo pathway proteins, in cells of growing Drosophila organs, in real time. This will provide novel insights into normal organ growth and pathogenic organ growth in diseases such as cancer.
Dr Mohammad Haskali (New Investigator, Sole CI - $614,077) Development of Innovative Foldamers for the Peptide Receptor Radionuclide Therapy of Tumours Overexpressing Cholecystokinin-2 Receptors. Summary: Peptide Receptor Radionuclide Therapy (PRRT) is a systematic treatment used to deliver high levels of radiation to cancer using radiopharmaceuticals known as theranostic agents (TAs). Until now TAs have been limited to only a few cancer types. This project aims to develop TAs to treat cancers which overexpress an important molecular target known as Cholecystokinin-2 (CCK-2) receptors. These TAs will be prepared in an innovative manner to display high affinity and stability for CCK-2 receptors.
Dr Marian Burr (New Investigator, Sole CI - $679,920) Restoring MHC class I antigen presentation to enhance anti-tumour immunity. Summary: Immune checkpoint inhibitor (ICI) therapies boost the immune response against cancer cells and have been very effective in treating certain types of cancer. Unfortunately not all cancers respond to ICIs and a common cause of resistance is failure to express a molecule called MHC class I, which allows the tumour to hide from immune cells. This project will identify ways to restore MHC class I to the surface of resistant tumours to promote elimination by the immune system following ICI therapy.
Prof David Bowtell (With Dr Liz Christie (CIB) - $1,137,742) Molecular and spatial characterization of drug resistance in human ovarian cancer. Summary: Ovarian cancer is the most deadly gynecologic cancer in Western women. Although initially responsive to chemotherapy, drug resistance commonly evolves in a matter of months. We previously documented novel mechanisms of drug resistance in the most common form of ovarian cancer and in this study we will map their distribution within patients. We will also investigate mechanisms of resistance to a new important class of anti-cancer drugs in ovarian cancer, the PARP inhibitors.
Prof Sherene Loi (With A/Prof Paul Neeson (CIB) - $765,117) Tissue resident memory T cells- delineating their role in breast cancer anti-tumor immunity. Summary: High levels of immune infiltrate in breast cancers has been shown to be associated with improved survival. It is unknown if simply quantity dictates prognosis or if there are important qualitative differences. We have identified a specific T cell immune subset that we believe is critical to anti-tumour immune responses. This project will delineate this population in greater detail as well as understand the cues that attract and draw in this critical immune population into breast cancers.
Prof Robert Ramsay (With Prof Sandy Heriot (CIC) and Dr Vignesh Narasimhan (CID) - $1,399,877) From the Stone Age to the State of the Art – Multidimensional Precision Medicine for Peritoneal CRC. Summary: Peritoneal cancer develops in the abdomen and may be present at primary diagnosis but can also arise from tumour cells that remain post-surgery or indeed they are mobilized by surgery. It is extremely difficult and expensive to treat and is rapidly fatal compared to most other cancers. We will use genetics, immunology assays, pre-clinical models with national and international collaborations to reduce, treat and cure peritoneal cancer and will test whether we can change clinical practice.
Prof Michael Henderson (With Dr David Gyorki (CIB) - $2,766,610) Melanoma Margins Trial-II: A Phase III, Multi-centre Randomised Controlled Trial Investigating 1cm vs 2cm Wide Surgical Excision Margins for AJCC Stage II Primary Cutaneous Melanoma (MelMarT-II). Summary: Primary melanomas (PM) are routinely excised with a wide margin to prevent recurrence. For patients with higher risk PM, there is debate as to the extent of the excision margin. We propose a 1cm margin will achieve equivalent survival outcomes to the recommended 2cm margin for patients with higher risk PM, while improving quality of life and reducing costs to the community. This trial will benefit patients worldwide, influencing care, clinical practice and future treatment guidelines.
Prof Richard Pearson (With Dr Elaine Sanij (CIB) - $900,028) Targeting nucleolar DNA damage response as a novel therapeutic strategy for high grade serous ovarian cancer. Summary: New therapies are required to improve outcomes for patients with ovarian cancer. In this proposal, we will optimise and validate the effectiveness of a new class of drugs we have discovered and developed to selectively damage the DNA of cancer cells, resulting in death of the cancers while sparing normal tissue.
Prof Grant McArthur (With Dr Karen Sheppard (CIB) - $1,527,367) Inhibition of PRMT5 as a cancer therapy. Summary: This proposal is aimed at improving the clinical benefit of BRAF/MEK and CDK4 inhibitors by combining with PRMT5 inhibition and extending these combination therapies into cancers with poor outcomes (pancreatic and oesophageal). These studies will provide mechanistic insight into the action of PRMT5 inhibitors in RAS/RAF/CDK4 driven tumours and identify patients that will likely benefit from PRMT5 therapy including combination therapy.
Prof Sarah-Jane Dawson (With Prof Ben Solomon (CIB) - $985,472) Monitoring evolutionary trajectories in non-small cell lung cancer to improve treatment outcomes. Summary: The expanding repertoire of treatment options in lung cancer is bringing into focus the need for improved ways to accurately monitor treatment responses and guide treatment decisions. Many cancers shed small amounts of DNA (ctDNA) into the bloodstream and changes in ctDNA levels have potential to be used as specific markers of response to cancer therapy. This project will evaluate novel strategies to directly guide treatment decisions in patients with lung cancer.
Prof Bernhard Riedel (With Prof Sandy Heriot (CIC) - $4,880,484) Volatile Anaesthesia and Perioperative Outcomes Related to Cancer (VAPOR-C Trial). Summary: Our laboratory research confirms clinical observations that gas anaesthetics increase the risk of cancer relapse. We propose a large, international, randomised trial to answer the important question of whether anaesthesia impacts long-term cancer-free survival in patients having cancer surgery. Our clinical trial will research whether an alternative widely used intravenous anaesthetic (propofol) and a common pain medicine (lidocaine) reduces inflammation and thereby stops cancer relapse.
