A team of researchers, led by Peter Mac’s Prof Rod Hicks, has been awarded a $1.5 million grant from the US-based Neuroendocrine Tumour Research Foundation (NETRF) to study new treatment approaches for this rare and difficult to treat cancer.

The international NETRF grant will allow a team of Peter Mac-led researchers to investigate new ways to tackle neuroendocrine tumours (NETs) using cutting-edge peptide receptor radionuclide therapy (PRRT) combined with different types of drugs in the hope of improving survival of people with NET.

NETs are a group of cancers arising from the nerve-like hormone-producing cells of the body. NETs can form from a range of different tissue types including pancreas, gut and lung.

While these cancers are relatively rare, many NET patients present with advanced disease for which treatment options are limited.

The new study will build on previous work into the use of drugs to sensitive cancers to PRRT, established by Prof Rod Hicks, Peter Mac’s Director of the Centre for Cancer Imaging, Head of the Molecular Imaging and Targeted Therapeutic Laboratory and Co-Chair of the Neuroendocrine Service, and Dr Shahneen Sandhu, clinician researcher and Medical Oncologist at Peter Mac.

“I am really excited about this grant because it is built on more than two decades of clinical and laboratory research in neuroendocrine tumours,” says Prof Hicks.

“Our success in attracting such a large and important international grant recognises our innovation in the field and quality of our research.”

PRRT uses small peptides bound to radioactive particles that recognise a specific protein, in this case the SSTR2 protein, displayed on the surface of cancer cells. Radiation is thus delivered in high doses directly to the tumour with relatively few side effects.

“This form of therapy has provided major advances in the treatment of NETs, reflected by year-on-year growth in referrals. Last year Peter Mac delivered close to 500 cycles of this treatment. However, responses to PRRT can vary greatly from disappearance of widespread disease in exceptional cases to complete resistance to treatment in others,” explains Prof Hicks.

Genetic factors, particularly the ability of cancer cells to repair damage to DNA, may underpin at least some of the resistance.

The research team will study the mechanisms of this resistance, including testing new combinations of PRRT with drugs that inhibit the process of DNA-repair.

To achieve this, the project will bring together experts from across Australia and New Zealand, including Dr Price Jackson whose medical physics program will provide tools that allow the accurate measurement of radiation dose to tumours, and Dr Richard Tothill and Assoc Prof Kaylene Simpson who will perform sophisticated genomic studies to identify genetic signatures associated with response to PRRT.

These studies will be supported by the expertise of the University of Melbourne's Prof Sean Grimmond, a world authority on NET genomics, and genomics and clinical experts from the University of Auckland, Prof Cris Print and Dr Ben Lawrence.

In parallel, pre-clinical testing of new drug combinations with PRRT will be undertaken by Dr Carleen Cullinane, and a clinical trial of a novel combination therapy will be led by Dr Grace Kong from Cancer Imaging and Assoc Prof Michael Michael from Medical Oncology at Peter Mac. Dr Sandhu will provide her expertise to the final design and implementation of the clinical study.

“We thereby expect to enhance the selection of patients for PRRT and to develop new combinations of PRRT with drugs that will further improve responses to this emerging treatment for patients with advanced neuroendocrine tumors,” says Prof Hicks.

“This project highlights Peter Mac’s holistic approach to research, combining strong fundamental science with translational research and clinical expertise, and leveraging both internal expertise and links with external collaborators. To me, it is emblematic of all that Peter Mac stands for.”