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.
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.
Using Bioengineered 3D Models To Replicate The Tumour Microenvironment In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$339,658.00
Summary
The research will address the poor prognosis of patients with advanced prostate cancer bone metastasis by establishing a novel 3D bioengineered bone model containing high amounts of fat cells, where cancer cells can relocate. This approach will help identifying the impact of fat cells on cancer cell function, and help determine whether fat cells are legitimate therapeutic targets, ultimately assisting clinicians to select better therapies for prostate cancer bone metastasis.
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.
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.
Characterising The Tumour Suppressive Function Of Myoepithelial Cell Stefin A In Ductal Carcinoma In Situ
Funder
National Health and Medical Research Council
Funding Amount
$474,840.00
Summary
Ductal carcinoma in situ (DCIS) is a pre-invasive stage of breast cancer, whereby the tumour cells remain restrained by myoepithelial cells that surround breast ducts. Predicting which cases of DCIS will later develop invasive cancer is difficult, meaning that the majority of patients have treatment. Stefin A is a protease inhibitor in myoepithelial cells shown to block cancer invasion and we aim to test the function of this protein in DCIS and its potential as a prognostic marker.
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.
Defining The Function Of ROCK In Establishing A Tumour-promoting Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$611,950.00
Summary
Cancer’s spread from its primary to secondary sites causes most cancer-related deaths. As cancers grow and spread, their internal structure is modified. Immune cells within the cancer begin to behave differently to the same types of cells in normal tissues, promoting its spread. We have discovered that many of these changes are regulated by a protein called ROCK. We plan to study how ROCK controls such a wide range of tumour promoting processes.
The Microenvironmental Niche In Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
It is well accepted that the cells in the local environment of cancers can help to promote the growth and spread of tumour cells. We have shown that a cell type known as the pericyte previously thought to be involved in controlling tumour expansion by affecting new blood vessel formation, may directly influence tumour growth, a notion that will be tested in human skin and ovarian cancer models. We will also test if pericyte markers can predict those cancer patients at greater risk of relapse.
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.