Identifying Resistance Mechanisms Of Targeted BRAF Inhibitors In Metastatic Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$379,015.00
Summary
Late-stage melanoma is an aggressive skin cancer for which traditional treatment strategies such as chemotherapy are ineffective. Recently, a new class of targeted drugs (BRAF inhibitors) has become the standard of care for a subset of melanoma patients; however, long term treatment success is complicated by drug resistance. This study will identify the causes of resistance with the purpose to improve targeted drug strategies and increase survival rates for late-stage melanoma patients.
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.
Harnessing Endogenous L1-mediated Mutagenesis To Elucidate New Candidate Genes For Liver Cancer
Funder
National Health and Medical Research Council
Funding Amount
$632,656.00
Summary
Retrotransposons are mobile genes that copy-and-paste themselves in our genome. Previously thought to represent “junk DNA”, retrotransposons are increasingly recognised to play major roles in biology. In a recent publication in Cell, we found that retrotransposons were highly active in some types of liver cancer, mutating key genes required to block tumour formation. In the current study, we will determine in greater depth how, and how often, these genes are involved in other types of liver canc ....Retrotransposons are mobile genes that copy-and-paste themselves in our genome. Previously thought to represent “junk DNA”, retrotransposons are increasingly recognised to play major roles in biology. In a recent publication in Cell, we found that retrotransposons were highly active in some types of liver cancer, mutating key genes required to block tumour formation. In the current study, we will determine in greater depth how, and how often, these genes are involved in other types of liver cancer.Read moreRead less
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.
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
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.
Defining Genomic Mechanisms Associated With Treatment Response, Drug Resistance And Early Blast Crisis In Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Chronic myeloid leukaemia is a fatal disease if untreated. Most patients now survive with new drugs, but some still rapidly die. I aim to understand these differences by investigating the genetic makeup of patients at diagnosis. Some may have gene mutations that prevent drugs from working effectively. Mutations will be detected using technology that can search more than 30,000 genes at the same time. This work could lead to improved survival for more patients by finding new targets for therapy.
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.
Genetics And Genomics Of Breast And Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$714,745.00
Summary
Our knowledge of the number and nature of the genes involved in breast and ovarian cancer is limited. To rapidly define the critical breast and ovarian cancer-causing genes my laboratory uses an integrative genomics approach whereby information from several genome-wide platforms are combined. A key initiative that will underpin much of our work is Lifepool, which is a unique cohort of 100,000 Victorian women attending BreastScreen that will support a range of research into breast cancer.
Next-generation Sequencing Of Candidate Ovarian Tumour Suppressor Genes
Funder
National Health and Medical Research Council
Funding Amount
$101,899.00
Summary
In Australia in 2001 there were approximately 1300 new cases of ovarian cancer. Survival of ovarian cancer is very poor and current treatments inadequate. To develop more effective treatments we need to understand the molecular events that cause ovarian cancer. Some genes are inactivated by loss of a copy or mutation. We aim to find these genes using new DNA sequencing techniques.