Mutational Signatures Of DDT: The Role Of A Controversial Persistent Endocrine Disrupting Pollutant On Prostate Cancer Aetiology
Funder
National Health and Medical Research Council
Funding Amount
$991,000.00
Summary
No carcinogen or prevention has been identified for prostate cancer (PCa). As carcinogens are commonly mutagens, we will use genomic interrogation to determine if extensive use of the hormone-disrupting pesticide DDT during the 40's to late 80's increased PCa globally. Having access to prostate tumours from men with biochemically confirmed lifelong DDT-exposure, will provide a measurable genomic signature to evaluate the impact of DDT globally, including Australia.
Understanding Tumour Plasticity And The Microenvironment Using Single-cell Technologies To Identify Novel Targets For Metastatic Castration-resistant Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$653,578.00
Summary
Most prostate cancer patients respond well to treatment, but some develop metastatic disease and respond poorly. During metastasis the cancer spreads to multiple organs and new combinations of genes become activated, making it difficult to develop new treatments. We will investigate these patterns of activation of genes in metastatic samples and how the immune system interacts with the cancer. We will use computational models to identify new drug targets and evaluate immunotherapy as an option.
Engineering CYP17A1 Inhibitors For Castrate-resistant Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$519,428.00
Summary
As prostate cancer progresses it becomes resistant to first line treatments and the current second line treatments have untoward side effects. This proposal will provide proof of principal for new selective drugs to be developed. We propose an innovative strategy to develop new selective drugs for the treatment of prostate cancer. This new therapeutic approach will identify new compounds for patients specifically with castrate sensitive and resistant prostate cancer.
Ovarian cancer is difficult to diagnose, patients present at a late stage of disease and it responds poorly to therapy. To improve treatment, it is crucial to gain new insights into ovarian cancer biology. We discovered a new protein, interferon epsilon, which is produced naturally by cells lining the female reproductive tract where it protects against infections and may even prevent development of cancers. We plan to characterise the action of IFNe on HGSOC and how best to use it for therapy.
From Functional Genomics To Precision Medicine: Identifying The Cause And Finding Optimal Therapy For Oral Squamous Cell Carcinoma
Funder
National Health and Medical Research Council
Funding Amount
$855,992.00
Summary
There is an alarming increase in mouth cancer in young patients who have never smoked. This is a debilitating and potentially fatal cancer without many treatment options. If the patient survives, the quality of life is usually very poor. Our team of medical, genetic, and mathematics experts are dedicated to finding the cause, and developing new treatments, for young non-smoking patients affected by this devastating cancer.
Hijacking A Death Switch In Pancreatic And Lung Cancer Cells To Develop A Novel Therapy
Funder
National Health and Medical Research Council
Funding Amount
$738,947.00
Summary
Pancreatic (PC) and lung (LC) cancer have a high mortality rate and poor response to current treatments. We have identified a protein whose inhibition in both PC and LC cells sensitises them to a cancer-cell specific therapy called TRAIL and switches signals that normally promote tumour growth into tumour death signals. This project aims to develop a novel therapeutic that inhibits our target and delivers TRAIL to PC and LC tumours, and could potentially improve survival for PC and LC patients.
Targeting Nerves In Tumours To Enhance Anti-cancer Immunity
Funder
National Health and Medical Research Council
Funding Amount
$1,090,190.00
Summary
The cancer journey is an incredibly stressful experience for patients. We discovered that stress stops immune cells and helps cancer spread. The goal of this study is to reveal how stress signals alter anti-cancer immunity and impacts cancer treatments. We will use elegant tools from neuroscience and immunology to define if blocking stress helps the immune cells that kill cancer and explore how blocking stress can improve standard anti-cancer drugs, including chemotherapy and immunotherapy.
Stopping Breast Cancer Progression By Targeting Tumour Stroma
Funder
National Health and Medical Research Council
Funding Amount
$772,877.00
Summary
Our latest research demonstrated that CRELD2 protein that is secreted by breast cancer cells alters normal cells surrounding tumour. CRELD2 represents an ideal therapeutic target as it is not important for normal cells and it is a secreted protein and thus can be targeted by numerous means. Successful completion of this research proposal will provide foundation to find new targets for combining therapies affecting both tumour and it's altered environment in breast and potentially other cancers.
The Ins And Outs Of Endocytosis Inhibition: Providing Diverse Opportunities For Treatment Of Incurable Cancers
Funder
National Health and Medical Research Council
Funding Amount
$912,353.00
Summary
The best new immune system anti-cancer drugs only work in ~30% of patients. We found a way to move the drug targets around in people's tumours temporarily to reverse resistance and have tested this in clinical trials. Here we propose to use immunology and the world's frontier electron microscope techniques to work out exactly what is happens to the tumours, immune cells and anti-cancer drugs when they interact in real clinical situations. The aim is to reach at least 60% patient response rate.
Oncogenic Determinants Of The Immune Response In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$588,144.00
Summary
There is an urgent need to develop new therapies for patients with AML. We have shown that the body's own immune system can target certain types of AML. We will determine how these types of AML change to escape control from the immune system and how this can be reversed to re-engage the anti-AML immune response. Using patient samples, we will determine how the anti-AML immune response changes during the course of standard therapy in order to best combine it with immune-targeted therapies.