Phosphatidylinositol 3-kinase Mutations Associated With Ovarian, Colon And Breast Tumours
Funder
National Health and Medical Research Council
Funding Amount
$154,000.00
Summary
Colorectal and breast cancers are the two most common registrable cancers in Australia and are second only to lung cancer in the total number of cancer deaths each year (4,678 and 2,612 deaths in 1997 for colorectal and breast, respectively). Ovarian cancer kills a further 740 women each year (Source: Cancer in Australia 1997, AIHW and AACR 2000). Thus, on average, one Australian dies of colorectal, breast or ovarian cancer every hour! Clearly, these are major diseases with a significant impact ....Colorectal and breast cancers are the two most common registrable cancers in Australia and are second only to lung cancer in the total number of cancer deaths each year (4,678 and 2,612 deaths in 1997 for colorectal and breast, respectively). Ovarian cancer kills a further 740 women each year (Source: Cancer in Australia 1997, AIHW and AACR 2000). Thus, on average, one Australian dies of colorectal, breast or ovarian cancer every hour! Clearly, these are major diseases with a significant impact on our society. Unfortunately, though, we still do not understand the basic molecular and-or biochemical abnormalities that initiate and-or drive the development of these cancers. Recent functional and genetic studies in a number of different tumour types (including colon and ovarian) have suggested that members of the phosphatidylinositol 3-kinase (PI3K) enzyme family may be oncogenes (cancer-causing genes). However, strong evidence confirming a causal role for PI3K in human cancer is yet to be reported. Our research proposal outlines a study to address this issue. We have preliminary data demonstrating mutations in at least one member of this enzyme family in a number of tumours. We now propose to undertake a comprehensive analysis of the spectrum, and frequency, of PI3K mutations that occur in colon, breast and ovarian tumours. These studies will allow us to make a definitive assessment of the role of PI3K in the development human cancer. In addition to furthering our understanding of the processes involved in the initiation and progression of human tumours, this project also has the potential to identify new markers for the early detection of cancer and novel targets for new anti-cancer therapies.Read moreRead less
SNAC2: A Randomised Trial Of Extending Sentinel Node Based Management To Women With Larger Or Multifocal Breast Cancers
Funder
National Health and Medical Research Council
Funding Amount
$1,266,430.00
Summary
SNAC2 extends the work begun in SNAC1, which recruited 1,088 women over 4 years. SNAC1 will determine if sentinel node biopsy causes less arm problems than axillary clearance. The goal of SNAC2 is to establish the risk of local recurrence and long term safety of sentinel node biopsy, especially for women with larger or multiple tumours. SNAC2 is needed to determine whether the smaller operation gives cure rates as good as axillary clearance. If it does, then it will become standard practice.
SNAC1:A Randomised Trial Of Sentinel Node Based Management Versus Axillary Clearance For Women With Small Breast Cancers
Funder
National Health and Medical Research Council
Funding Amount
$1,338,436.00
Summary
SNAC1 compares two operations for assessing cancer spread to the lymph nodes in women with early breast cancer: 1) axillary clearance and 2)sentinel node biopsy. Axillary clearance involves removal of most lymph nodes in the armpit. In sentinel node biopsy only a few lymph nodes most closely related to the breast cancer are removed. The trial will determine if sentinel node biopsy reduces lymphoedema and gives equivalent cure rates. If it does, then it should become standard practice.
SNAC1:A Randomised Trial Of Sentinel Node Based Management Versus Axillary Clearance For Women With Small Breast Cancers
Funder
National Health and Medical Research Council
Funding Amount
$240,187.00
Summary
Over 13,000 ANZ women are diagnosed with breast cancer each year. Most need surgery to remove the cancer and determine if it has spead to glands in the armpit (axillary lymph nodes). Knowing whether the cancer has spread to the axillary lymph nodes helps determine prognosis and plan treatment. Surgical removal is the most reliable way to assess the axillary lymph nodes. SNAC1 compares two operations for assessing cancer spread to the lymph nodes in women with early breast cancer: 1) axillary cle ....Over 13,000 ANZ women are diagnosed with breast cancer each year. Most need surgery to remove the cancer and determine if it has spead to glands in the armpit (axillary lymph nodes). Knowing whether the cancer has spread to the axillary lymph nodes helps determine prognosis and plan treatment. Surgical removal is the most reliable way to assess the axillary lymph nodes. SNAC1 compares two operations for assessing cancer spread to the lymph nodes in women with early breast cancer: 1) axillary clearance and 2) sentinel node biopsy. Axillary clearance involves removal of most lymph nodes in the armpit. In sentinel node biopsy only a few lymph nodes most closely related to the breast cancer are removed. Axillary clearance is the current standard operation. However, it is associated with risks including infection, pain, stiffness, numbness and lymphoedema (arm swelling). Lymphoedema may occur in 5-50% of women treated for breast cancer and can cause major suffering and disability. In many women their breast cancer has not spread to the lymph nodes, and axillary clearance is unnecessary. Recent studies suggest sentinel node biopsy may provide as much information as axillary clearance. Scans and dye are used to help locate the sentinel nodes. Minimising the amount of surgery to the armpit should reduce the side effects. However, the long term safety and effectiveness of removing only a few nodes is unknown. The trial will determine if sentinel node biopsy reduces lymohoedema and gives equivalent cure rates. If it does, then it should become standard practice. The study complements comparable studies being done in US, UK and Europe by providing unique information about arm symptoms and quality of life. SNAC1 recruited 1,088 women in 4 years. This application is for the work needed to report on outcomes after all women have been followed for 5 years.Read moreRead less
Tailored Treatments For Premenopausal Women With Endocrine Responsive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$299,213.00
Summary
For women <50yrs with ER+ breast cancer adjuvant treatment (AT) with chemotherapy (CT), tamoxifen and ovarian function suppression (OFS) are each effective and reduce recurrence. Combining 2 treatments is more effective than 1, but it is unclear if combining 3 provides any extra benefit. 2 trials,SOFT and TEXT, aim to answer this question. SOFT tests the benefit of adding OFS for very young women who remain premenopausal after CT, TEXT is for women who should receive OFS from the start of AT.
Quality Of Life And Arm Symptoms Following Axillary Surgery For Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$32,003.00
Summary
The aim of this project is determine how best to measure, analyse and compare the effects of different operations for women with breast cancer. This will be done with information on measurements of arm swelling, symptoms, functions, and other aspects of quality of life collected in over 1,000 women taking part in a national randomised trial. This research will provide important information about the effects of these operations, and about how best to design future surgical trials.
The Role And Inheritance Of Constitutional Epimutations In Early-onset Colorectal Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$347,551.00
Summary
Traditionally familial cancers are thought to be caused by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that chemical attachments to one gene (MLH1) stops it working, even where there is no spelling mistake, and that those chemical changes can be inherited in families with bowel cancer. We will determine how frequently this type of defect occurs in bowel cancer patients, how and why it arises, and if other cancer genes are similarly affected.
The Assessment Of Clinical And Molecular Adjunctive Tools For The Early Detection Of Oral Mucosal Neoplasia
Funder
National Health and Medical Research Council
Funding Amount
$454,383.00
Summary
It is anticipated that this research will make a significant contribution to our understanding of the natural development of oral cancer and will thus have a direct benefit to patients. The proposed research will enable high quality genetic analysis of individual mutations of relevance to oral cancer via a rapid, reliable, economic, and sensitive screening assay for the assessment of a large number of suspicious oral mucosal lesions.
Epimutations As Germ-line Defects In Hereditary Cancer Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$385,925.00
Summary
Traditionally familial cancers were thought to be caused and inherited by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that a 'chemical coat' around the MLH1 gene, causing it to be switched off, can also be inherited in some cases of bowel cancer, without any mistakes within the gene's code. We will determine if this 'coat' causes other types of cancer and if this runs in families. We also hope to find out how the coat is formed and may be reversed.
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