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.
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
The Role Of Centromere Defects In Cancer Formation And Progression
Funder
National Health and Medical Research Council
Funding Amount
$601,386.00
Summary
When cells divide, their DNA must be copied and distributed faultlessly into the new cells. Defects in the factors that control this process will result in serious health problems including cancer. The objective of this project is to identify what these factors are and study how they contribute to cancer. Results gained from this project are expected to significantly increase our understanding of how cancer cells control the replication of their DNA and therefore their own fate.
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.
For 60 years, we have had only 3 effective cancer treatments: surgery, radiation and chemotherapy, often used in combination.The last 5 years have produced a powerful fourth treatment: the patient's own immune system.The long standing collaborations and synergies of our multi-disciplinary teams have already underpinned many recent advances in immune-based therapies: we are now poised to develop several further immunotherapies and on track to test them in patients during the term of this grant.
Role Of LncRNA IDH1-AS1 In Regulating C-Myc Driven-glycolysis And Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$685,043.00
Summary
It is thought that understanding cancer metabolism will reveal vulnerabilities that can be exploited in the clinic. Indeed, compared to most normal cells, cancer cells utilise different fuels to sustain proliferation and to adapt to their environment. Herein we have discovered a molecular switch that regulates the key metabolic enzyme IDH1 and show this controls tumour growth. Given this switch may be active in 50% of cancers we anticipate our work will have significance to many cancer types.
Role Of Proline-rich Tyrosine Kinase 2 (Pyk2) In Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$85,254.00
Summary
Ovarian cancer is one of the most lethal gynaecological cancers in the developed world. Elevated levels of gonadotropin hormones and cell protein Pyk2 have been implicated in ovarian cancer. Our aim is to determine the role of Pyk2 in growth and metastasis of ovarian cancer when stimulated with gonadotropins. In addition, we aim to identify protein changes which occur in ovarian cancer when stimulated by gonadotropins in order to identify new biomarkers for the disease.
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