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.
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.
Elucidating The Role Of Claudin-2 In Tumour Initiation And Metastasis Development From Colorectal Cancer: Consequence For Tumour Relapse
Funder
National Health and Medical Research Council
Funding Amount
$398,993.00
Summary
Mortality from colorectal cancer is often due to the development of metastases. Cancer stem cells (CSC) are suspected to provide a major drive for metastasis development, to resist current therapies, and to initiate tumour relapse. Yet, little is known about mechanisms that control CSC behaviour. Our project investigates the role of claudin-2, a cell adhesion protein that is strongly overexpressed in colorectal cancer, in the regulation of CSCs, metastasis development and tumour relapse.
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.
A Randomised Phase III Study Of The Duration Of The Anti-PD1 - Therapy In Metastatic Melanoma (STOP-GAP)
Funder
National Health and Medical Research Council
Funding Amount
$2,308,600.00
Summary
PD-1 inhibitors turn on the immune system,so that it can fight the cancer cells in the body and are effective in Melanoma. This study investigates whether interrupted PD-1 inhibitor dosing has no worse Melanoma outcome than continuous treatment for 24 months, which may lead to a reduction in treatment-related toxicities, improvements in patients' quality of life and decrease the cost of treatment to the health system as well as individual. Results may inform treatments for other common cancers.
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.