The Nature And Significance Of Clonal Evolution In Human Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$665,420.00
Summary
Cancers can progress in patients by developing genetic changes that favor the growth, survival and spread of cancer cells. However, the rate at which genetic changes occur in human cancer is not known. This project will determine the degree and biological significance of genetic change in human melanoma by using a novel method of growing tumors from single cells and comparing genetic differences between them.
Understanding And Targeting Acquired Chemoresistance In High-grade Serous Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$527,824.00
Summary
We recently discovered a mutation in recurrent high-grade serous ovarian cancer that causes profound overexpression of the multidrug resistance pump, MDR1 (Patch et al Nature 2015). In this study I will explore approaches to reverse drug resistance caused by this mutation in recurrent ovarian cancer with a view to utilising alternative treatments to improve patient outcomes.
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
Understanding The Function Of Recql4 In DNA Replication And Genome Maintenance
Funder
National Health and Medical Research Council
Funding Amount
$698,447.00
Summary
We are interested in understanding how cancer forms. We are using information from human cancers to understand how a protein causes cancer. We are using models to understand how mutations in this protein give rise to bone cancer. These models are used together with detailed biochemistry to understand how the mutations affect protein function.
Use Of Circulating Tumour DNA To Characterise The Mutational Landscape Of Marginal Zone Lymphoma, Monitor Treatment Response And Detect Emergence Of Resistance
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Marginal zone lymphoma (MZL) is a subtype of B-cell non-Hodgkin lymphoma for which the molecular drivers of disease are poorly understood. We hypothesise that circulating tumour DNA may be ideal for characterising the genetic mutations that underpin MZL, monitoring treatment response and detecting emergence of resistance. This non-invasive method of disease monitoring has the potential to transform management of cancers such as MZL, identify new treatment options and improve survival outcomes.
mTOR signalling in serous ovarian cancer. Serous ovarian cancer is the most aggressive and lethal gynaecological cancer in Australian women. Activation of Mammalian Target of Rapamycin (mTOR) is frequently observed and associated with poor prognosis in ovarian cancer patients. However, the mechanisms dysregulating mTOR in the pathogenesis of ovarian cancer are unknown. In preliminary studies, deletion of genes regulating mTOR signalling in up to 60 per cent of human serous ovarian cancer patien ....mTOR signalling in serous ovarian cancer. Serous ovarian cancer is the most aggressive and lethal gynaecological cancer in Australian women. Activation of Mammalian Target of Rapamycin (mTOR) is frequently observed and associated with poor prognosis in ovarian cancer patients. However, the mechanisms dysregulating mTOR in the pathogenesis of ovarian cancer are unknown. In preliminary studies, deletion of genes regulating mTOR signalling in up to 60 per cent of human serous ovarian cancer patients was observed. This project will provide mechanistic details of involvement of mTOR signalling in pathogenesis of the serous ovarian carcinoma, and develop a rationale for targeting mTOR pathway in these patients. Read moreRead less
Therapeutically Exploiting Non-oncogene Addiction And Defining Genetic Interactions For Disease Progression In A Preclinical Model Of Inflammation-dependent Gastric Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$624,960.00
Summary
Cancers of the stomach are often associated with chronic inflammation and represent a major health burden with little treatment options available. We propose to test whether drugs undergoing clinical testing for other diseases may have beneficial effects in a preclinical model of gastric cancer, and establish the genetic interaction required for gastric cancer progression. The study outcomes may highlight novel therapeutic opportunities for the clinic.
The Fellowship would support Professor Bowtell, one of the world’s leading ovarian cancer researchers. His work focuses on clinical problems of chemotherapy resistance and the development of new therapeutic approaches. His studies are underpinned by the Australian Ovarian Cancer Study (AOCS), one of the world’s most sophisticated clinical cohort studies of ovarian cancer, with over 3000 Australian women enrolled.
Functional Studies On The Role Of DNp73 In Stem Cells And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$428,838.00
Summary
This project investigates the role of the p73 gene in regulating stem cells and facilitating intestinal cancer formation. We hypothesize that when a particular form of this gene (DNp73) is upregulated it prevents differentiation of stem cells and promotes tumour formation. We combine novel approaches in mice and fruit flies to examine the function of DNp73 in stem cells with analysis of human tumour samples. These studies may identify a new target for tumour therapy.