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Improving The Treatment For Childhood Cancer: Neuroblastoma As A Model
Funder
National Health and Medical Research Council
Funding Amount
$5,029,092.00
Summary
One in three children with cancer still die of their disease, and side-effects of treatment are considerable. Over the past 15 years, the Chief Investigators have established themselves as a leading international research group in child cancer and have successfully applied their laboratory-based discoveries to improve the clinical management of children with malignant diseases. In particular, key advances have been made in basic cell biology, molecular biology and in defining clinically relevant ....One in three children with cancer still die of their disease, and side-effects of treatment are considerable. Over the past 15 years, the Chief Investigators have established themselves as a leading international research group in child cancer and have successfully applied their laboratory-based discoveries to improve the clinical management of children with malignant diseases. In particular, key advances have been made in basic cell biology, molecular biology and in defining clinically relevant molecular targets and prognostic indicators for the child cancer, neuroblastoma, the commonest solid tumour in young children. These findings have been made possible by the team assembling, over recent years, an extensive and unique range of in vitro and in vivo model systems, together with a large bank of clinical neuroblastoma specimens. In this research program, the team members propose an experimental approach that will continue their studies, focussing on cancer initiation and better target identification within cancer cells, leading to the development of effective and non-toxic novel compounds, possibly prevention strategies,and introduction of novel therapies into clinical trial.Read moreRead less
Tailored Treatments For Premenopausal Patients With Endocrine Responsive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$257,250.00
Summary
For women under 50 years with hormone receptor positive (ER+) breast cancer, adjuvant treatment with chemotherapy, tamoxifen and ovarian ablation are each effective and reduce recurrence. Combining two treatments is more effective than one, although it is uncertain if combining three provides extra benefit. Ovarian ablation by surgery or radiation is permanent, but reversible ovarian suppression by injections is now available. Three international trials called SOFT, TEXT and PERCHE have been des ....For women under 50 years with hormone receptor positive (ER+) breast cancer, adjuvant treatment with chemotherapy, tamoxifen and ovarian ablation are each effective and reduce recurrence. Combining two treatments is more effective than one, although it is uncertain if combining three provides extra benefit. Ovarian ablation by surgery or radiation is permanent, but reversible ovarian suppression by injections is now available. Three international trials called SOFT, TEXT and PERCHE have been designed for adjuvant therapy of premenopausal women with ER+ breast cancer. These trials take into account regional-country variations in medical practice and different patient choices in this setting. SOFT is for very young women and tests the benefit of adding ovarian suppression in a woman who has received chemotherapy, with tamoxifen planned, but who has not gone into menopause after chemotherapy. The trial also tests if substituting a newer drug called exemestane for tamoxifen, combined with ovarian function suppression is more effective. TEXT is for women who would ordinarily be treated with ovarian suppression plus tamoxifen. The TEXT trial also tests substitution of exemestane for tamoxifen. Exemestane is an aromatase inhibitor. Aromatase inhibitors lower oestrogen levels, but only work if the ovaries are inactive. Recent trials in post menopausal women show aromatase inhibitors are more effective than tamoxifen, and we aim to replicate that improvement in younger women by combining exemestane with ovarian suppression. PERCHE is for women in whom the benefit of chemotherapy is uncertain, for example those with limited or no spread to lymph nodes. All women receive combined endocrine treatment with ovarian suppression plus tamoxifen, and are randomised to receive in addition, either chemotherapy or no chemotherapy, to see if results differ.Read moreRead less
DNA methylation-based diagnosis of cancer and identification of novel therapeutic targets. In our aging society, cancer represents a severe economic and quality-of-life threat. DNA methylation switches genes off, and recently, it was shown that defects in DNA methylation contribute to human diseases including cancer. This project will identify defects in DNA methylation associated with cancer. Identifying these defects will enable us to design non-invasive, early diagnostic tests for cancer on b ....DNA methylation-based diagnosis of cancer and identification of novel therapeutic targets. In our aging society, cancer represents a severe economic and quality-of-life threat. DNA methylation switches genes off, and recently, it was shown that defects in DNA methylation contribute to human diseases including cancer. This project will identify defects in DNA methylation associated with cancer. Identifying these defects will enable us to design non-invasive, early diagnostic tests for cancer on blood or bodily excretions, and to pursue novel therapeutic approaches for treating cancer. The expected outcomes would generate exports to markets in the USA and Europe and replace imports of drugs and technology to treat cancer.Read moreRead less
Inhibition Of Breast Cancer Metastasis Through Targeting Of Laminin-10 Function
Funder
National Health and Medical Research Council
Funding Amount
$391,241.00
Summary
Breast cancer affects 1 in 11 women in Australia. Whilst breast cancer is highly curable when detected early, current treatments are ineffective when the disease has spread to other organs such as bone and lungs. Thus, novel therapies for the treatment of advance disease are urgently needed. We have found that laminin-10, a protein present in the breast and thought to control normal breast development and maturation, is particularly abundant in aggressive tumours as well as in those that have sp ....Breast cancer affects 1 in 11 women in Australia. Whilst breast cancer is highly curable when detected early, current treatments are ineffective when the disease has spread to other organs such as bone and lungs. Thus, novel therapies for the treatment of advance disease are urgently needed. We have found that laminin-10, a protein present in the breast and thought to control normal breast development and maturation, is particularly abundant in aggressive tumours as well as in those that have spread to bone and lungs suggesting that this protein may play a role in the dissemination of breast cancer cells to other organs. Consistent with this, we have found that laminin-10 stimulates breast tumour cell adhesion and movement in culture, two activities required for successful metastasis of tumour cells. The overall objective of the projects is to demonstrate that breast cancer metastasis can be inhibited by interefering with the function of laminin-10. To this end, we will measure the effect of blocking the production of LN-10 in breast tumour cells on their ability to metastasise. Alternatively, we will test fragments of laminin-10 for their ability to block laminin-10-induced tumour cell growth and movement (required for their escape from the breast) and viability (required for their establishment in distant organs). We will generate antibodies against the most inhibitory fragments and test their effect on spontaneous metastasis in a clinically relevant mouse model of breast cancer metastasis in an attempt to stop-reverse the progression of the disease. If successful, this project will provide the foundation for the development novel inhibitors targeting laminin-10 for the treatment of patients with advanced breast cancer.Read moreRead less