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.
Prognostic Importance Of Androgen Receptors In Epithelium And Stroma In Early Stage Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$348,750.00
Summary
The use of serum prostate specific antigen (PSA) to screen asymptomatic men for prostate cancer has reduced the stage of disease at diagnosis. The majority of tumours are now small and potentially organ-confined. The use of nomograms, algorithms based on preoperative clinical features of these patients (serum PSA level, Gleason grade, clinical stage) has facilitated this process, but is imperfect as 20-30% of patients experience disease relapse within 5-7 years. Tumours with similar preoperative ....The use of serum prostate specific antigen (PSA) to screen asymptomatic men for prostate cancer has reduced the stage of disease at diagnosis. The majority of tumours are now small and potentially organ-confined. The use of nomograms, algorithms based on preoperative clinical features of these patients (serum PSA level, Gleason grade, clinical stage) has facilitated this process, but is imperfect as 20-30% of patients experience disease relapse within 5-7 years. Tumours with similar preoperative clinical features have markedly different outcomes, reinforcing the inadequacy of current approaches to determining whether or not an individual patient has organ-confined disease. A new approach is to incorporate into the standard diagnostic nomograms, biological features from preoperative core biopsy linked to the process of disease relapse, and which independently predict patient outcome risk group. Our preliminary studies using a small hypothesis-generating cohort of patients with early stage prostate cancer determined that elevated levels of androgen receptors (AR) in malignant epithelial cells and reduced levels of AR in peritumoral stromal cells independently predict disease relapse after surgery. In this project, AR measurements will be analysed in independent cohorts of patients derived from two Australian institutions to determine whether the predictive value is maintained across multi-Institutional cohorts. Selected androgen-regulated markers of tumour growth and spread (proliferative, apoptotic, metastatic) will be examined in microarrayed postoperative tissue samples. The postoperative markers will be examined for independence of prediction of relapse. Independent markers will be examined for ability to increase predictive efficacy in standard diagnostic nomograms. Levels of the two markers with greatest predictive value will be measured in preoperative core biopsies and tested for predictive ability as a prelude to clinical practice.Read moreRead less
Combining Laboratory And Computational Approaches To Develop Reliable Low Cost HIV Prognostics
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Certain anti-HIV drugs called "CCR5 antagonists" block HIV entry into immune cells. However, HIV drug-resistance can occur. Globally, patient access to CCR5 antagonists has been limited because the pre-treatment laboratory test required to determine HIV drug-resistant is expensive and time-consuming. My research will lead to development of computer programs that reliably, rapidly and cheaply determine HIV drug-resistance and thus greatly improve patient access to CCR5 antagonists worldwide.
Novel Methods For Early Bedside Detection And Prognosis Of Preterm Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$630,880.00
Summary
Quick and robust assessments of preterm brain activity are critical for identifying early markers of brain injuries. We need to predict poor outcomes before they develop in order to give clinicians the best chance of helping sick infants. This project will develop and validate new non-invasive methods for assessing early brain activity in preterm infants at risk of developing poor neurodevelopmental outcomes.
Circulating Tumour DNA As A Marker Of Complete Pathological Response And Long Term Outcome For Locally Advanced Rectal Cancer Treated With Pre-operative Chemoradiotherapy
Funder
National Health and Medical Research Council
Funding Amount
$613,183.00
Summary
Rectal cancers are often treated by chemoradiotherapy (CRT) followed by surgery which may result in long-term stoma. A significant proportion of these patients can achieve complete remission to CRT alone. This project will assess the accuracy of a promising blood marker (circulating tumour DNA) for predicting response to treatment in patients with rectal cancer undergoing CRT. If confirmed to be a reliable marker, this test could be used to select patients who may be able to avoid or delay surge ....Rectal cancers are often treated by chemoradiotherapy (CRT) followed by surgery which may result in long-term stoma. A significant proportion of these patients can achieve complete remission to CRT alone. This project will assess the accuracy of a promising blood marker (circulating tumour DNA) for predicting response to treatment in patients with rectal cancer undergoing CRT. If confirmed to be a reliable marker, this test could be used to select patients who may be able to avoid or delay surgery.Read moreRead less
Gastric Cancer: Early Detection Of Disease, Relapse And Prediction Of Extent Of Disease
Funder
National Health and Medical Research Council
Funding Amount
$421,800.00
Summary
Gastric cancer (GC) is the second commonest cause of cancer in the world. The mainstay of treatment for GC is surgical resection, but despite improvements in surgical interventions the mortality rate remains high. The 5 year survival rate of GC is about 30% over 5 years. Accurate staging is fundamental to the management of GC and current investigations are inadequate. It has become possible to measure the activity of thousands of genes to identify those genes that predict whether a patient will ....Gastric cancer (GC) is the second commonest cause of cancer in the world. The mainstay of treatment for GC is surgical resection, but despite improvements in surgical interventions the mortality rate remains high. The 5 year survival rate of GC is about 30% over 5 years. Accurate staging is fundamental to the management of GC and current investigations are inadequate. It has become possible to measure the activity of thousands of genes to identify those genes that predict whether a patient will survive or succumb to their disease. We propose to use gene expression profiling to predict the risk of recurrence of gastric cancer in patients. We will examine over 270 tumours and use an independent group of patients to evaluate the test. We aim to develop a test that will help the clinician decide the type of surgical resection to perform or whether to give adjuvant chemotherapy. The test may also guide the use of more specific anticancer drugs. Early detection of GC is very important because patients with early stage GC have better outcome. We have already analysed over 60 GC tumours with microarrays and found genes that are specifically expressed by the tumours that are potential candidates as cancer markers. We plan to examine more cases of GC, both to find more genes and validate our candidate genes as tumour markers. We also want to look for patterns of proteins in blood of patients that identifies GC and use this pattern to follow patient progress to treatment.Read moreRead less
MICRORNA PREDICTORS OF OESOPHAGEAL TUMOUR RESPONSE TO CHEMOTHERAPY AND RADIOTHERAPY
Funder
National Health and Medical Research Council
Funding Amount
$659,990.00
Summary
Chemoradiotherapy (CRT) is used for the treatment of oesophageal cancer before surgical resection, and for patients not undergoing surgery. However, it is unsuccessful for many, causing side effects, no clinical gain, and delaying surgery. MicroRNAs are small molecules that control cellular functions. This project will identify miRNA markers which are able to predict cancer response to CRT, and this will help clinical decision making for individualized treatment.
Prognostic Factors Following A First Episode Of Central Nervous System Demyelination Suggestive Of Multiple Sclerosis.
Funder
National Health and Medical Research Council
Funding Amount
$719,475.00
Summary
Multiple sclerosis is the second most common cause of neurological morbidity in young Australians after trauma. Knowing who will progress to develop multiple sclerosis after a first attack and at what rate they will progress is an important question as it will allow us to target treatment to those at greatest risk and modify a person's lifestyle to reduce the risk of developing MS or slow their rate of progression.
Androgen-regulated Proteins: Predictors Of Prostate Cancer Development And Progression
Funder
National Health and Medical Research Council
Funding Amount
$391,073.00
Summary
Use of PSA (prostate specific antigen) levels in blood to screen for prostate cancer has resulted in a) earlier detection of tumours and b) increased diagnosis of a premalignant disease of the prostate called PIN (prostatic intraepithelial neoplasia). PIN is thought to progressively change into cancer, which can invade the rest of the body. Growth of the cells of the prostate is regulated by male hormones called androgens. Small cancers localised to the prostate grow in response to androgens, bu ....Use of PSA (prostate specific antigen) levels in blood to screen for prostate cancer has resulted in a) earlier detection of tumours and b) increased diagnosis of a premalignant disease of the prostate called PIN (prostatic intraepithelial neoplasia). PIN is thought to progressively change into cancer, which can invade the rest of the body. Growth of the cells of the prostate is regulated by male hormones called androgens. Small cancers localised to the prostate grow in response to androgens, but larger cancers which have spread from the prostate grow steadily even after the androgen supply is cut off by removal of the testicles. In this project we will examine changes in the level of various proteins in the prostate, which are known to be produced in response to androgen, to see whether they discriminate: 1) those patients with PIN who will go on to develop prostate cancer, 2) those patients with small cancers within the prostate who progress to widespread cancer. We also propose to use a laser-controlled dissecting microscope to obtain pure populations of cancer cells from prostate tissues and then to isolate their DNA in order to: a) examine the DNA sequence of the protein which controls cellular growth in response to androgen (ie the androgen receptor) to see whether undesirable changes (mutations) have occurred in its structure during the development of the cancer, and b) identify proteins which mediate the effects of the androgen regulated proteins and control cancer development or spread. This will be done using the revolutionary technique of gene microarrays, where partial DNA sequences of approximately 4,000 different prostate genes are spotted onto small membrane filters, and which enable identification of genes that change in level with the onset of cancer and cancer spread. These 2 objectives will, in the case of a) prevent inappropriate treatment for prostate cancer, and b) identify targets for new treatments and for chemoprevention.Read moreRead less