SOFT And TEXT Premenopausal Randomised Adjuvant Endocrine Breast Cancer Trials.
Funder
National Health and Medical Research Council
Funding Amount
$722,380.00
Summary
SOFT and TEXT trials enrolled premenopausal women with hormone-sensitive early breast cancer to assess if post-operative hormone treatment that included ovarian function suppression plus tamoxifen, or an aromatase inhibitor exemestane, could improve outcomes. Initial results indicate fewer breast cancer recurrences with the treatment combination of ovarian suppression plus exemestane as compared with tamoxifen, and follow-up of women in these trials can show if overall survival can be improved.
Randomised Phase II Trial Of Neoadjuvant Chemotherapy +/- Concurrent Aromatase Inhibitor Endocrine Therapy To Down-stage Large Oestrogen Receptor Positive Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$2,302,496.00
Summary
Women diagnosed with large oestrogen receptor positive breast cancer are often treated with chemotherapy before surgery to reduce the size of the cancer, while treatment to lower oestrogen levels is given after surgery. This trial is studying if combining chemotherapy with oestrogen lowering treatment before surgery will better shrink the cancer which can improve the surgery options.
Endocrine Therapy Tolerance As A Cancer Cell Survival Mechanism For Late Recurring Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$450,083.00
Summary
~25% of breast cancer deaths are attributable to cancers that have failed endocrine therapy and recur >5 years after primary diagnosis. These cancers are not well understood because their long latency makes them difficult to study. We have new models of this disease that identify a “therapy tolerant” population, and this is likely to re-emerge to cause late recurrence. Our work could potentially identify new biological tests and therapeutic strategies to treat late recurring breast cancer.
Role Of Cyclin E2 In Hormone-responsive Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$328,194.00
Summary
The female hormone estrogen stimulates the growth of breast cancers by promoting cell reproduction. We have found that cyclin E2, which is part of the machinery that controls cell reproduction, responds to estrogen. Since abnormally high levels of cyclin E2 are linked with earlier relapse in breast cancer, we wish to understand what role it plays in estrogen action and in breast cancer, how its levels are controlled, and whether too much cyclin E2 interferes with drugs that block estrogen action
Prevention Of Late Breast Cancer (BC) Events In Postmenopausal Women With Endocrine Responsive BC.
Funder
National Health and Medical Research Council
Funding Amount
$4,687,599.00
Summary
This proposal is from Australia's national breast cancer (BC) trials group, the ANZ BCTG, for a new phase III, multi-centre clinical trial evaluating whether much later endocrine therapy with an aromatase inhibitor can prevent BC recurrence in postmenopausal women who have: had hormone sensitive BC at least 6 years ago; were treated by Tamoxifen more than 1 year ago; and, are currently disease free. Subjects will randomly receive letrozole or placebo as a daily tablet for five years.
Exploring A New Way To Overcoming Endocrine Resistance In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$441,764.00
Summary
Despite significant improvements in long-term outcome with the use of endocrine therapy (such as tamoxifen and letrozole), breast cancer remains the most common cause of cancer-related death amongst Australian women. A major clinical problem limiting the effectiveness of endocrine therapy is tumour resistance, either intrinsic or acquired. Indeed, about half of patients immediately fail to respond to the treatment, while in the initially responding patients the tumours ultimately progress to res ....Despite significant improvements in long-term outcome with the use of endocrine therapy (such as tamoxifen and letrozole), breast cancer remains the most common cause of cancer-related death amongst Australian women. A major clinical problem limiting the effectiveness of endocrine therapy is tumour resistance, either intrinsic or acquired. Indeed, about half of patients immediately fail to respond to the treatment, while in the initially responding patients the tumours ultimately progress to resistance to the drug leading to the disease relapse. Therefore, it is imperative to better understand the mechanisms responsible for the resistance and to explore new strategies that overcome this clinical problem in order to prolong the overall survival of patients with breast cancer. Our recent work have shown that a recently-identified enzyme, termed sphingosine kinase, plays an important role in promoting breast cancer cell growth. We also found that cells that have a high level of the enzyme had bad outcomes in response to anti-estrogen drug, tamoxifen. Thus this project seeks to identify the role of this enzyme in contributing towards drug resistance, and test if inhibition of this enzyme could improve and-or restore the drug response in breast cancer. It will ultimately pave a new way to overcoming the drug resistance for improving the treatment and prevention of breast cancer.Read moreRead less
The Mechanism Of Growth Hormone Receptor Activation
Funder
National Health and Medical Research Council
Funding Amount
$679,500.00
Summary
Growth hormone GH excess or deficit results in considerably shortened lifespan. While cardiovascular disease is a major element in this mortality, GH status has also been linked to kidney disease and diabetic retinopathy. Importantly, GH produced locally in breast cells and prostate cells transform s these cells, creating cancers. We aim to define how GH activates its receptor, to facilitate a GH antagonist which results from understanding how GH activates its cell surface receptor.
Validating A New Model For Growth Hormone Receptor Activation
Funder
National Health and Medical Research Council
Funding Amount
$472,500.00
Summary
Growth hormone is an important hormone therapeutic for treating dwarfism. Recently, many new therapeutic applications for growth hormone have been discovered, particularly in relation to its anabolic actions. These include post surgery recovery, enhanced bone fracture healing, Crohns disease, dilated cardiomyopathy, infertility and ageing. The hormone exerts these actions through its receptor, which is a class1 cytokine receptor, similar to many receptors important in regulating immunity, inflam ....Growth hormone is an important hormone therapeutic for treating dwarfism. Recently, many new therapeutic applications for growth hormone have been discovered, particularly in relation to its anabolic actions. These include post surgery recovery, enhanced bone fracture healing, Crohns disease, dilated cardiomyopathy, infertility and ageing. The hormone exerts these actions through its receptor, which is a class1 cytokine receptor, similar to many receptors important in regulating immunity, inflammation, metabolism and cancers. In principle, if we can find out how the GH receptor works, this information would help in designing drugs to treat many immune and inflammatory disorders. With current NHMRC support we have developed a model which describes how GH activates the receptor at a molecular level. The model involves two pre-associated receptors at the cell surface binding to the hormone, with the result that the receptors are rotated relative to each other, and this brings the two JAK2 signalling units attached tothe receptor inside the cell into alignment, so they can activate each other. We can activate the receptor without hormone by artificially rotating it. This model is a prediction based on several techniques, but lacks proof of rotation. There are also a number of issues relating to the need for rigidity in the receptors, so the torque can be transmitted into the cell, since many believe there is no rigidity just above the membrane. We predict there is , but need to prove this. This information is vital for designing small orally active mimics of growth hormone, and for developing GH antagonists, likely to be useful for breast and colon cancer. Finally, we have evidence that the specificity of receptor signalling can be changed by mutating the outer part of the receptor (novel). We believe this can be used to change the activity spectrum of GH, hence decrease side effects, by developing analogs which activate one pathway or the other.Read moreRead less