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 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.
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.
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.
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.
Defining The Role Of The PSA-related Kallikrein Serine Proteases In Hormone Dependent Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$880,454.00
Summary
Kallikreins are a family of 15 proteins, related to the prostate cancer biomarker PSA, that have potential as biomarkers for hormone dependent cancers such as prostate and ovarian cancer. Prof Judith Clements and her team discovered that kallikreins induce resistance to chemotherapy in ovarian cancer and are found in prostate cancer bone disease. Her research will determine the underlying mechanisms of kallikrein action and their potential as new biomarkers or treatment targets for these disease ....Kallikreins are a family of 15 proteins, related to the prostate cancer biomarker PSA, that have potential as biomarkers for hormone dependent cancers such as prostate and ovarian cancer. Prof Judith Clements and her team discovered that kallikreins induce resistance to chemotherapy in ovarian cancer and are found in prostate cancer bone disease. Her research will determine the underlying mechanisms of kallikrein action and their potential as new biomarkers or treatment targets for these diseases.Read moreRead less
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.
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.
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.