Defining Stromal-Cancer Cell Interactions For Xenografting Human Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$559,635.00
Summary
Prostate Cancer research continues to be hindered by a lack of laboratory models to understand disease progression and design new drugs to cure the disease. In this study, we propose to use a new and reliable method of growing human prostate cancer tissue in mice. Using this model, we will investigate the role of hormone signalling and cellular communication in prostate cancer that may lead to new therapies for men diagnosed with organ-confined disease.
The behaviour of prostate cancer cells is regulated by their surrounding environment known as the stroma. The stroma has been proposed as a therapeutic target, but it is a diverse mix of cells that needs to be specifically targeted. Not all stromal cells are equal; cells surrounding tumours have different features from cells in normal tissue. Therefore, the goal of this project is to directly isolate cancer-associated stromal cells from patient tissue and study their role in cancer progression.
The Microniche: A Novel In-vitro And In-vivo Prostate Cancer Model System
Funder
National Health and Medical Research Council
Funding Amount
$561,012.00
Summary
Maintaining primary prostate cancer cells (PCa) in vitro remains an enormous challenge for the field, and this obstructs efforts to systematically characterize cell behaviour and quantify drug response. Our group recently developed a 3-demsensional (3D) organoid culture system that does maintain PCa in vitro, and here we will integrate this technology with our 3D bone maorrow niche model system to better characterize PCa bone metastases and identify new clinical treatment regimes.
Identifying Castrate-resistant Tumour Cells In Localised Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$573,047.00
Summary
This proposal addresses one of the most important challenges in cancer: what cell population ‘drives’ tumour progression, and how can it be effectively targeted? We will define the prostate cancer cells that survive androgen withdrawal therapy and investigate new ways to target them. Eliminating these important cells earlier in disease progression will lead to increased survival for men with prostate cancer.
Novel Targeting Of Therapy-resistant Prostate Cancer Cells.
Funder
National Health and Medical Research Council
Funding Amount
$596,978.00
Summary
Prostate cancer is treated by removing male hormones (androgens). Although the bulk of the tumour regresses, some cells remain and the cancer often grows back in an aggressive form. We will study new ways to eliminate therapy resistant cancer cells and thereby provide more lasting treatments for prostate cancer. Ultimately, we hope to inform the design of ground-breaking clinical trials that could re-shape the treatment paradigm of advanced prostate cancer.
Each year, 18,000 Australian men are diagnosed with prostate cancer. While current treatments are designed to directly target cancer cells, the tumour-associated stroma is also recognised to play a pivotal in the establishment and progression of prostate cancer. This grant aims to investigate the contribution of stromal Hedgehog signalling, with the view to creating new treatment strategies that will treat the entire tumor environment.
Fatty Acid Elongation: A Novel Target For Prostate Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Lipids are a class of molecules that make up cell membranes and are an important source of energy for cells. Changes in lipids occur during prostate cancer progression, most prominently in a process called fatty acid elongation, which requires enzymes called elongases. This project will seek to better understand the consequences of lipid elongation in prostate cancer cells, its potential role in therapy resistance, and whether the elongase enzymes can be targeted as new therapies.
Understanding the mechanisms in the development of mutations in cancers will assist in development of targeted therapies to overcome chemotherapy resistance. The recently discovered TMPRSS2:ERG fusion in prostate cancer is unique as dominant fusion translocations are uncommon in solid organ malignancy. Activation induced cytidine deaminase (AID) is thought to play a role. Understanding the role of AID and downstream DNA repair pathways may be a target for future therapies in cancer.
Development Of Effective Biomarkers For The Diagnosis And Prognosis Of Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,062,585.00
Summary
Every year ~20,000 Australian men are diagnosed with prostate cancer and more than 3,000 die of this disease. The current PSA test for the diagnosis of prostate cancer is not specific and this can result in incorrect diagnosis, unnecessary biopsies and lead to wrong treatments. We have discovered a novel change in the biology of prostate cancer. We will use this information to develop new tests for prostate cancer, which provide early accurate detection and can predict disease progression.
Endosomal Reactive Oxygen Species In Tumour Angiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$633,739.00
Summary
Cancer claims more lives worldwide than any other disease affecting millions of people annually. Tumours grow and spread in the body by acquiring their own blood vessels that provide them with nutrients and oxygen. We have identified a new protein called NADPH oxidase that promotes the development of these new blood vessels in tumours. We propose to test new drugs that block NADPH oxidase activity to stop the development of new blood vessels for the potential treatment of cancer