A Genomic Approach Towards An Understanding Of Clonal Evolution And Disease Progression In Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$671,689.00
Summary
Cancer development is associated with changes in the genetic composition of the cell. These changes involve the loss/gain of genetic material and/or changes in gene expression. Using sophisticated technology, we will define the changes in the genes that are associated with the transition from a benign to a malignant cancer state. We will examine this process in the blood cancer, multiple myeloma, in order to identify new treatment targets for this incurable disease.
The Mutagenic Influence Of 5-methylcytosine And Its Relevance For Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$844,462.00
Summary
Over time our cells accumulate damage to their DNA, which introduces mistakes in the genetic code. These mistakes can alter genes that regulate cell growth and survival and, in this way, they begin the process of turning a normal cell into a cancer. This research is investigating the cellular repair mechanisms that safeguard against DNA damage. Manipulating these repair mechanisms may offer a new way to treat cancer, by selectively inducing DNA damage within cancer cells.
Identification Of Genes Responsible For Familial Predispositions To Haematological Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$713,944.00
Summary
A successful approach to the identification of cancer genes has been to study the 5-10% of cases that occur in families with an inherited predisposition to develop cancer. In contrast to solid tumors, few cancer-causing germ-line mutations have been identified for hematological cancers. We are using cutting edge technologies to identify blood cancer genes in a collection of both Australian and international families and comparing them to similar sporadic cancers.
This study will address the idea that cancer commonly involves a genetic pathway that is normally used by stem cells to proliferate in an undifferentiated state. We have evidence to indicate that this system is active in cancer cells and believe this could explain how cancer cells manage to divide rapidly in a primitive state. This project may bring a new perspective to the study of malignant transformation and has the potential to reveal multiple new targets for cancer therapy.
Somatic Retrotransposition Drives Neoplastic Mutagenesis In Glioblastoma Multiforme
Funder
National Health and Medical Research Council
Funding Amount
$667,342.00
Summary
Retrotransposons are mobile genes that copy-and-paste themselves in our genome. Previously thought to represent “junk DNA”, retrotransposons are increasingly found to play major roles in biology. In a recent landmark publication in Nature, we demonstrated that retrotransposons move in the healthy human brain. In the current study, we will use cutting-edge technologies to determine whether brain cancer can occur as a result. This will provide new perspectives of the genetic basis for cancer.
Circulating Tumour DNA As A Noninvasive Biomarker In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$1,299,114.00
Summary
The expanding repertoire of treatment options in melanoma is bringing into focus the need for improved ways to accurately monitor treatment responses and guide treatment decisions. Many cancers shed small amounts of DNA (ctDNA) into the bloodstream and changes in ctDNA levels have potential to be used as specific markers of response to cancer therapy. This project will evaluate if ctDNA can be used as a form of ‘liquid biopsy’ to guide treatment decisions in patients with melanoma.
A Comprehensive Genomic Analysis Of Oesophageal Adenocarcinoma: Understanding The Genetic Aetiology Of OAC Towards Biomarkers Of Progression, Prognosis And Targeted Treatment.
Funder
National Health and Medical Research Council
Funding Amount
$987,906.00
Summary
Oesophageal cancer (OAC) continues to have poor survival despite surgery, chemotherapy and radiotherapy. Selecting patients for the most appropriate therapies and improving survival remain unmet research needs. We propose to undertake a detailed genetic study of OAC, including “next generation” sequencing, in order to catalogue the genetic changes in the disease. This information forms an essential basis for identifying genetic signatures of OAC progression, prognosis and treatment response.
Molecular Determinants Of Susceptibility And Progression In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$6,006,551.00
Summary
Breast cancer is heterogeneous, making management a challenge. High-grade cancers including the ‘basal’ type are aggressive, often found in young women and have a propensity for distant spread. They are also associated with a BRCA1 gene mutation. We will study mechanisms that predispose some women to develop breast cancer, the process that allows cancers to grow at distant sites such as the brain and lungs, and how DNA repair proteins are implicated. This will allow development of new diagnostic ....Breast cancer is heterogeneous, making management a challenge. High-grade cancers including the ‘basal’ type are aggressive, often found in young women and have a propensity for distant spread. They are also associated with a BRCA1 gene mutation. We will study mechanisms that predispose some women to develop breast cancer, the process that allows cancers to grow at distant sites such as the brain and lungs, and how DNA repair proteins are implicated. This will allow development of new diagnostic tools and treatments.Read moreRead less
Personalised Biomarkers In Breast Cancer Using Circulating Tumour DNA
Funder
National Health and Medical Research Council
Funding Amount
$231,060.00
Summary
The measurement of tumour specific circulating DNA in the blood of women with breast cancer has the potential to be utilised as a personalised biomarker and revolutionise the management of this disease. This project aims to improve our understanding of the relationship between circulating tumour DNA, the progression of cancer, and responses to cancer treatment. Furthermore, it aims to address how this new tool can be integrated into clinical practice to provide benefits for women with breast can ....The measurement of tumour specific circulating DNA in the blood of women with breast cancer has the potential to be utilised as a personalised biomarker and revolutionise the management of this disease. This project aims to improve our understanding of the relationship between circulating tumour DNA, the progression of cancer, and responses to cancer treatment. Furthermore, it aims to address how this new tool can be integrated into clinical practice to provide benefits for women with breast cancer.Read moreRead less
Defining The Genomic And Therapeutic Landscape Of Familial Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,146,096.00
Summary
As a cancer develops it accumulates alterations (mutations) in its DNA. Some of these alterations lead to enhanced tumour growth, whilst others provide insight into normal processes that have gone wrong to enable the tumour to arise. We will use DNA sequencing and mathematical approaches to characterise these alterations and to identify therapeutic targets in breast tumours arising in patients with an inherited predisposition to develop cancer.