An International Whole Genome Study To Definitively Map Heritable Risk In Sarcomas
Funder
National Health and Medical Research Council
Funding Amount
$836,550.00
Summary
We want to understand why some people get sarcomas, and others do not. This is likely due to genetic causes, because these cancers affect the young. We now have the tools to address this question, and have created the largest and best characterised study of sarcoma families in the world upon which to apply these tools. This project will create an enduring foundation for research into the genetic basis of sarcomas for the next 20 years.
Tracking The Origins And Drivers Of Metastasis In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,022,600.00
Summary
Prostate cancer is now the most commonly diagnosed cancer but only 10% of men with it, will die from it. Our current ability to discriminate between cancers with an indolent course and those that are lethal is poor. This project will examine the mixture of tumour clones (subclones) that are present in prostate cancers and define and track those cancer subclones that break away from the prostate and lodge in distant sites, causing death.
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.
A Vulvar Cancer Cluster Caused By Genetic Susceptibility: Investigating The Genetic Mechanism.
Funder
National Health and Medical Research Council
Funding Amount
$1,154,342.00
Summary
Cancer of the vulva is 70 times more common in young Aboriginal women in Arnhem Land than in other women. Human Papillomavirus (HPV), which also causes cervical cancer, is the usual cause of this cancer; initial investigations have found that HPV is present in these cancers but is not the reason for the excessive incidence. This study will investigate inherited risk factors contributing to the development of this disease in this population.
Identification And Molecular Characterisation Of High-risk Premalignant Breast Lesions
Funder
National Health and Medical Research Council
Funding Amount
$560,382.00
Summary
Understanding the full repertoire of genetic events that underlie the development of breast cancer may allow development of prevention strategies. This study will analyse genetic data of benign breast lesions that may be non-obligate precursors of breast cancer. Importantly, clinical management of these lesions is difficult. A reliable method of predicting the risk of progression to cancer would be a significant advance, with benefits to individual patients and also the health system.
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.
Circulating Tumour DNA Analysis Of Acquired Treatment Resistance In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$511,807.00
Summary
Taxanes are commonly used chemotherapeutic agents in breast cancer, yet treatment resistance remains a significant clinical problem for which new approaches are needed. Many cancers shed small amounts of DNA (circulating tumor DNA (ctDNA)) into the bloodstream, and analysis of ctDNA can allow assessment of tumour specific genomic changes occurring during treatment. This project aims to utilise ctDNA to study acquired treatment resistance to taxane-based chemotherapy in metastatic breast cancer.
Genetic And Genomic Dissection Of Polycomb Repressive Complex 2 (PRC2) In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$576,598.00
Summary
The evolution of normal cells to cancer involves mutations that activate cancer-causing genes and/or prevent the actions of anti-cancer genes. It has become increasingly evident that cancer development also involves changes to epigenetic regulation, or control of gene activity by chemical modification of the gene or its environment rather that changes in DNA sequence. This project aims to explore the tumour suppressor activity of an important epigenetic regulatory complex in lymphoma.
Elf5 And The Basis For Antiestrogen Resistant Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,181,326.00
Summary
Resistance to anti estrogen therapies causes half of breast cancer deaths. We have recently discovered (Plos Biol 2012) that the transcription factor Elf5 is intimately involved in this process. This grant will develop our understanding of the transcriptional and genomic events involving Elf5 that lead to antiestrogen resistance and metatstasis, to develop new models of antiestrogen resistance, biomarkers that predict antiestrogen resistance and new therapeutic targets and strategies that preven ....Resistance to anti estrogen therapies causes half of breast cancer deaths. We have recently discovered (Plos Biol 2012) that the transcription factor Elf5 is intimately involved in this process. This grant will develop our understanding of the transcriptional and genomic events involving Elf5 that lead to antiestrogen resistance and metatstasis, to develop new models of antiestrogen resistance, biomarkers that predict antiestrogen resistance and new therapeutic targets and strategies that prevent antiestrogen resistance.Read moreRead less
Stress-induced Genomic Instability As A Driver Of Adaptive Responses In Human Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$690,426.00
Summary
Growing experimental evidence suggests human cancer cells use evolutionary conserved programs to regulate their mutation rates in response to pharmacological agents, accelerating adaptation and the emergence of resistance. The purpose of our study is to identify the common molecular pathways and genetic mechanisms driving the regulation of mutation rates. Targeting of these pathways using a new generation of “anti-evolution” drugs is an attractive possibility for novel therapeutic approaches.