Analysis Of Gene Amplification-loss And Methylation Associated With Progression To Metastatic Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$620,197.00
Summary
Many bowel cancers can be removed by surgery, but in many cases the cancer reoccurs. While chemotherapy can reduce the chance of recurrence, it can produce significant side effects. Currently there are few markers to indicate change of recurrence, therefore deciding who should, or should not receive chemotherapy is difficult to decide. This study will analyse differences in DNA from patients that do and do not relapse, to guide future decisions on patients who will benefit from chemotherapy.
Biomarkers Of Phenotype, Prognosis And Response To Therapy In Pancreatic Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$105,845.00
Summary
Pancreatic cancer (PC) is the 4th leading cause of cancer deaths in our society. This research is aimed at the discovery of novel biomarkers with the ability to forecast prognosis and response to treatments in patients with PC. Ultimately, this will lead to the “individualisation” of the treatment for each patient, so that the most appropriate therapy could be given to an individual patient. This would significantly improve the overall survival and the quality of life for patients.
Clinical Outcomes In Individuals With An Inherited Predisposition To Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$606,015.00
Summary
Genes have recently been identified which, when abnormal, result in an inherited tendency towards developing breast cancer (BC). It is now possible to undergo testing for abnormalities in these genes. However, there is little known about the best ways to prevent cancer or detect it early in individuals with such a gene abnormality. In addition, it is possible that BCs occuring in women with a gene abnormality might behave differently (have a different prognosis and thus require different treatme ....Genes have recently been identified which, when abnormal, result in an inherited tendency towards developing breast cancer (BC). It is now possible to undergo testing for abnormalities in these genes. However, there is little known about the best ways to prevent cancer or detect it early in individuals with such a gene abnormality. In addition, it is possible that BCs occuring in women with a gene abnormality might behave differently (have a different prognosis and thus require different treatment) from other BCs. Answers to these important questions are essential for women to be able to make informed decisions about how best to reduce their risk of developing, or dying from, BC. This study will examine the clinical outcomes of individuals (both those who have not yet developed cancer and those who have) with an inherited tendency to BC. The study has 2 components; each builds on one of 2 existing Australian studies of hereditary BC 1) Is the likely clinical outcome (prognosis) different for BC patients with a gene abnormality compared to those without? The cancer and treatment details of BC patients in Melbourne and Sydney who are already enrolled in the Australian Breast Cancer Family Study will be examined to determine whether those with a gene abnormality have a better or worse outcome than those without. 2) What factors impact on the clinical outcome (development of cancer) in well individuals with an inherited tendency to BC? An Australia-wide study of inherited BC (kConFab) has recruited families with a strong family history of BC. The family history, lifestyle, exposure to female hormones, cancer screening and preventive surgery details of all individuals in the study will be collected 3 years following study entry. Ultimately this information should help determine how best to prevent cancer in such individuals.Read moreRead less
Integrin Beta3 As A Therapeutic Target For Breast Cancer Metastasis To Bone
Funder
National Health and Medical Research Council
Funding Amount
$431,675.00
Summary
There are limited effective treatments for advanced breast cancer. The project investigates the role of a protein called integrin beta3 in the spread of breast tumours to bone, the most common site of secondary tumour formation (metastasis) in breast cancer patients. We will determine if the presence of integrin beta3 in breast tumours identifies patients at risk of developing bone metastases and test novel drugs against integrin beta3 in mice.
BIOLOGICAL STUDIES OF A NEW RECURRENT FUSION GENE FOUND IN T-CELL LEUKAEMIA
Funder
National Health and Medical Research Council
Funding Amount
$187,925.00
Summary
Chromosome translocation, in which breaks occur in two chromosomes and rejoin to form two new hybrid chromosomes, is a common genetic alteration in leukaemia. Translocations have been invaluable in identifying genes important in the development of leukaemia. The genetic consequence of translocation is either the deregulation of critical genes adjacent to the breakpoints or the formation of new hybrid genes with novel properties. We have identified the genes at the breakpoints of a T-cell leukaem ....Chromosome translocation, in which breaks occur in two chromosomes and rejoin to form two new hybrid chromosomes, is a common genetic alteration in leukaemia. Translocations have been invaluable in identifying genes important in the development of leukaemia. The genetic consequence of translocation is either the deregulation of critical genes adjacent to the breakpoints or the formation of new hybrid genes with novel properties. We have identified the genes at the breakpoints of a T-cell leukaemia translocation involving chromosomes 4 and 11. The chromosome 11 gene, NUP98, is known to be involved in two other translocations in acute myeloid leukaemia but not in T-cell leukaemia. The chromosome 4 gene RAP1GDS has not been previously shown to be involved in human cancer. This project seeks to understand how the fusion protein NUP98-RAP1GDS (NRG) plays a role in the origin of leukaemia.Read moreRead less
Androgen-regulated Proteins: Predictors Of Prostate Cancer Development And Progression
Funder
National Health and Medical Research Council
Funding Amount
$391,073.00
Summary
Use of PSA (prostate specific antigen) levels in blood to screen for prostate cancer has resulted in a) earlier detection of tumours and b) increased diagnosis of a premalignant disease of the prostate called PIN (prostatic intraepithelial neoplasia). PIN is thought to progressively change into cancer, which can invade the rest of the body. Growth of the cells of the prostate is regulated by male hormones called androgens. Small cancers localised to the prostate grow in response to androgens, bu ....Use of PSA (prostate specific antigen) levels in blood to screen for prostate cancer has resulted in a) earlier detection of tumours and b) increased diagnosis of a premalignant disease of the prostate called PIN (prostatic intraepithelial neoplasia). PIN is thought to progressively change into cancer, which can invade the rest of the body. Growth of the cells of the prostate is regulated by male hormones called androgens. Small cancers localised to the prostate grow in response to androgens, but larger cancers which have spread from the prostate grow steadily even after the androgen supply is cut off by removal of the testicles. In this project we will examine changes in the level of various proteins in the prostate, which are known to be produced in response to androgen, to see whether they discriminate: 1) those patients with PIN who will go on to develop prostate cancer, 2) those patients with small cancers within the prostate who progress to widespread cancer. We also propose to use a laser-controlled dissecting microscope to obtain pure populations of cancer cells from prostate tissues and then to isolate their DNA in order to: a) examine the DNA sequence of the protein which controls cellular growth in response to androgen (ie the androgen receptor) to see whether undesirable changes (mutations) have occurred in its structure during the development of the cancer, and b) identify proteins which mediate the effects of the androgen regulated proteins and control cancer development or spread. This will be done using the revolutionary technique of gene microarrays, where partial DNA sequences of approximately 4,000 different prostate genes are spotted onto small membrane filters, and which enable identification of genes that change in level with the onset of cancer and cancer spread. These 2 objectives will, in the case of a) prevent inappropriate treatment for prostate cancer, and b) identify targets for new treatments and for chemoprevention.Read moreRead less
Dissecting The Function Of The Hedgehog-Patched Pathway In Breast Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$606,811.00
Summary
There have been significant improvements in survival from breast cancer, particularly due to specialised treatments that target faulty pathways in the growth of cancer cells. One newly described, aggressive type of breast cancer called basal-like breast cancer lacks specialised treatment. We will determine whether the 'Hedgehog' signalling pathway is a suitable target for basal breast cancer therapy.
Clinical Trial Of Adjuvant Docetaxel And Doxorubicin For Node Positive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$185,135.00
Summary
This project is investigating the optimal use of docetaxel and doxorubicin in the treatment of women with breast cancer and involved lymph nodes (N+). Every year 3000 women in Australia, and over 400,000 worldwide are newly diagnosed with N+ breast cancer. Using available treatments more than 60% of these (5 per day in Australia, 4,500 each week worldwide) will die from breast cancer. The efficacy of adjuvant chemotherapy in early breast cancer is well established by the international overview c ....This project is investigating the optimal use of docetaxel and doxorubicin in the treatment of women with breast cancer and involved lymph nodes (N+). Every year 3000 women in Australia, and over 400,000 worldwide are newly diagnosed with N+ breast cancer. Using available treatments more than 60% of these (5 per day in Australia, 4,500 each week worldwide) will die from breast cancer. The efficacy of adjuvant chemotherapy in early breast cancer is well established by the international overview conducted by the Early Breast Cancer Trialist's Collaborative Group (EBCTCG). They have demonstrated the efficacy of adjuvant chemotherapy on reducing mortality and recurrence rates, but current regimens are far from optimal. Docetaxel (Taxotere), a new agent, has effectiveness and manageable side effects in the treatment of advanced breast cancer patients, and can plausibly improve outcomes for patients with early N+ breast cancer by optimal integration into current adjuvant chemotherapy regimens. This clinical trial is designed to compare whether it is advantageous to use docetaxel and-or doxorubicin in combination or sequentially with other currently available chemotherapy drugs.Read moreRead less