Hormonal Influences In The Pathogenesis Of Ovarian Tumours
Funder
National Health and Medical Research Council
Funding Amount
$264,601.00
Summary
Ovarian cancer is one of the most common malignancies affecting the female reproductive system. We have found that two types of tumour of the ovary produce a hormone called inhibin; these tumours are also known to produce the steroid hormone estrogen. In these studies we are seeking to determine the genetic changes in the tumours that cause the production of these hormones. We suspect that these genetic changes are also the same changes which contribute to the development of the cancers. In orde ....Ovarian cancer is one of the most common malignancies affecting the female reproductive system. We have found that two types of tumour of the ovary produce a hormone called inhibin; these tumours are also known to produce the steroid hormone estrogen. In these studies we are seeking to determine the genetic changes in the tumours that cause the production of these hormones. We suspect that these genetic changes are also the same changes which contribute to the development of the cancers. In order to identify these genes we will draw on our knowledge of the genes that are important in the controlof growth and hormone secretion in normal ovarian cells. To assist this molecular analysis we will use two ovarian cell lines in culture that have many of the features of the primary tumours including inhibin secretion. We will also use new techniques to scan over 500 genes involved in tumours in general to see whether we detect any unusual or distinctive patterns in this sub-group of tumours. A genome wide scanning technique will be used to seek changes in the DNA of the tumours, inparticular loss of genetic material or amplification of regions. Identification of the genetic changes within these tumours should enable better systems of classification, enhance prognostication and provide specific targets for the development of appropriate treatment strategies.Read moreRead less
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.
Ovarian cancer is frequently fatal and an extremely distressing cause of death in women. Our research program draws on the Australian Ovarian Cancer Study (AOCS), involving over 2000 women with ovarian cancer to investigate the genetic causes, and molecular changes that control cancer growth and response to therapy. The program is part of Australia’s $27m commitment to the International Cancer Genomics Consortium, an ambitious, worldwide effort to map the cancer genome.
TRACEBACK - Identification Of Women Carrying Germline BRCA1/2 Mutations Through A Retrospective Analysis Of Patients Diagnosed With High Grade Serous Ovarian Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$83,284.00
Summary
Inheriting a mutated-BRCA is associated with significant risk of developing cancer. It is a crucial diagnosis to make with proven procedures that can reduce the risk of cancer developing. Ovarian cancer (HGSOC) is the tumour most strongly associated with BRCA (15-20%) and provides a diagnostic opportunity, but despite Australian guidelines <50% receive testing. Our aim is to provide BRCA1/2 screening opportunities to patients and families and improve the rate of BRCA testing Australia wide.
Engineering MYCN Models Of High-grade Serous Ovarian Cancer (HGSC)
Funder
National Health and Medical Research Council
Funding Amount
$797,478.00
Summary
The most lethal type of ovarian cancer, high-grade serous cancer (HGSC), can be divided into four subtypes based on gene patterns. One subtype involves a set of genes/proteins that, in their specific combination, result in activation of a pathway known as MYCN. As most HGSC start in the fallopian tube, we are using fallopian tube material to make new MYCN HGSC models to observe development in the earliest stages. We hope to generate new tests and treatments for this subtype of ovarian cancer.
The Role Of Primordial Follicle Activation In Premature Ovarian Failure
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
As women age, both the quality and quantity of their eggs decline and their chances of conceiving plummets. Premature ovarian failure (POF) is a disease of infertility, diagnosed in 3% of all women, defined by the early onset of menopause before age 40. Our poor understanding of the factors that regulate female egg supply remains a major limitation in treating POF. I will study key factors responsible for controlling egg number, with practical implications for POF diagnosis and treatment.
The Microenvironmental Niche In Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
It is well accepted that the cells in the local environment of cancers can help to promote the growth and spread of tumour cells. We have shown that a cell type known as the pericyte previously thought to be involved in controlling tumour expansion by affecting new blood vessel formation, may directly influence tumour growth, a notion that will be tested in human skin and ovarian cancer models. We will also test if pericyte markers can predict those cancer patients at greater risk of relapse.
The TERT Locus As A Susceptibility Gene For Ovarian And Breast Cancer: Genetic And Functional Evaluation
Funder
National Health and Medical Research Council
Funding Amount
$394,601.00
Summary
Breast and ovarian cancer, which are among the commonest cancers in Australian women, share similar causes. We have found that a gene involved in maintaining the ends of chromosomes increases risk of ovarian cancer. The project aims to explore this further, and also to determine whether it also increases risk of breast cancer.
Targetting Deregulated Signalling Pathways In High-grade Serous Ovarian Cancer: Defining Therapeutic Response And Mechanisms Of Resistance
Funder
National Health and Medical Research Council
Funding Amount
$641,263.00
Summary
Ovarian cancer is the major cause of death from gynaecological cancer. Most patients present with advanced disease and die of their cancer. This proposal aims to use new research detailing the common genetic changes in tumour samples and our extensive panel of ovarian cancer cell lines to identify new treatment options for specific types of ovarian cancer. We expect this will result in clinical trials of therapies selected based on the characteristics of an individual patient’s disease.
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.