Molecular Targeting To Telomerase And Cancer Cell Immortality By A Novel Inhibitor
Funder
National Health and Medical Research Council
Funding Amount
$430,812.00
Summary
Infinite growth of cancer cells is a hallmark of cancer. Telomerase is required for cancer cell immortality. Inhibition of telomerase may thus offer an opportunity to stop cancer cells. We have identified an inhibitor of telomerase. This project will study the mechanisms of action of the novel inhibitor, investigating how to control cancer cell immortality as a baseline for more applied anti-cancer therapeutic studies.
OVERCOMING RESISTANCE OF HUMAN MELANOMA TO CHEMOTHERAPY
Funder
National Health and Medical Research Council
Funding Amount
$499,500.00
Summary
Melanoma is the third most common cancer in women and men respectively. In NSW alone approximately 400 die each year from the disease. The main treatment of melanoma is surgical removal of the primary tumor on the skin but once the disease spreads beyond the skin to other organs there is no curative treatment. This study will identify whether resistance of melanoma to chemotherapy is due to failure to induce sufficient levles of pro-apoptotic BH3 only proteins and-or activation of apoptosis resi ....Melanoma is the third most common cancer in women and men respectively. In NSW alone approximately 400 die each year from the disease. The main treatment of melanoma is surgical removal of the primary tumor on the skin but once the disease spreads beyond the skin to other organs there is no curative treatment. This study will identify whether resistance of melanoma to chemotherapy is due to failure to induce sufficient levles of pro-apoptotic BH3 only proteins and-or activation of apoptosis resistance pathways. The results will be directly relevant to subsequent clinical trials in melanoma paients. Apoptosis may be triggered by chemotherapeutic agents but human melanoma shows wide variability in apoptotic responses to chemotherapy. Recent studies have shown that the Bcl-2 family of pro- and anti-apoptotic proteins and inhibitor of apoptosis proteins appear to be key regulators of the (mitochondrial) apoptosis pathway induced by chemotherapy. The activity of the proteins appear to be regulated by several signal pathways in the cell which may be activated by signals external or intrinsic to the cell. We wish to characterize the proteins involved in chemotherapy induced apoptosis, assess their variability between melanoma cells that are sensitive or resistant to apoptosis and characterize the signal pathways involved in regulating the proteins in human melanoma.Read moreRead less
Targeting Adaptive Mechanisms To Endoplasmic Reticulum Stress In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
Melanoma is a major Australian health problem, but there is no curative treatment once the disease spreads beyond the skin. We will study the role the response of melanoma cells to stress conditions of an organelle called endoplasmic reticulum in determining sensitivity of melanoma to killing induced by therapeutic drugs. If successful, this study will provide much needed new insights into the resistance of melanoma to treatment and point to new treatment approaches against the disease.
Predicting Response To Chemoradiotherapy In Patients With Advanced Rectal Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$461,605.00
Summary
Many cancer patients receive expensive and unpleasant therapies that actually do not benefit them. This project will use a new technology that can simultaneously assess the level of expression of thousands of genes. We will test if the pattern of gene expression in tumours can predict the patients' response to therapy. Success will significantly improve the clinical management of advanced cancer patients and provide a rational basis upon which to tailor individualized treatment regimes.
Downregulation Of N-myc Oncogene Expression As A Therapeutic Strategy For Childhood Neuroblastoma.
Funder
National Health and Medical Research Council
Funding Amount
$145,990.00
Summary
Neuroblastoma is a common cancer of young children which, despite the use of powerful anticancer drugs that cure other childhood cancers, has only a 40% survival rate. Many laboratories have shown that the most aggressive neuroblastoma tumours, which are most resistant to the action of anticancer drugs, have an abnormal number of copies of a cancer-associated gene, called N-myc. Patients whose tumours have multiple N-myc copies have dismal survival prospects, and new treatments for such patients ....Neuroblastoma is a common cancer of young children which, despite the use of powerful anticancer drugs that cure other childhood cancers, has only a 40% survival rate. Many laboratories have shown that the most aggressive neuroblastoma tumours, which are most resistant to the action of anticancer drugs, have an abnormal number of copies of a cancer-associated gene, called N-myc. Patients whose tumours have multiple N-myc copies have dismal survival prospects, and new treatments for such patients are urgently needed. Several studies, using models of neuroblastoma cells growing in the laboratory, have shown that it is possible to create small fragments of genetic material which can specifically switch off the N-myc gene. When this happens, the neuroblastoma cells behave in a less aggressive and malignant way. We have recently shown that these genetic fragments are capable of reducing the growth of tumours in mice which have been genetically manipulated to develop neuroblastoma. We now want to develop new types of genetic fragments (DNAzymes) that will be even more effective at switching off N-myc and inhibiting neuroblastoma development, because these fragments may be extremely valuable for treating neuroblastoma in patients.Read moreRead less
Hormonal Influences In The Pathogenesis Of Ovarian Tumours
Funder
National Health and Medical Research Council
Funding Amount
$264,601.00
Summary
Ovarian cancer is one of the most common malignancies affecting the female reproductive system. We have found that two types of tumour of the ovary produce a hormone called inhibin; these tumours are also known to produce the steroid hormone estrogen. In these studies we are seeking to determine the genetic changes in the tumours that cause the production of these hormones. We suspect that these genetic changes are also the same changes which contribute to the development of the cancers. In orde ....Ovarian cancer is one of the most common malignancies affecting the female reproductive system. We have found that two types of tumour of the ovary produce a hormone called inhibin; these tumours are also known to produce the steroid hormone estrogen. In these studies we are seeking to determine the genetic changes in the tumours that cause the production of these hormones. We suspect that these genetic changes are also the same changes which contribute to the development of the cancers. In order to identify these genes we will draw on our knowledge of the genes that are important in the controlof growth and hormone secretion in normal ovarian cells. To assist this molecular analysis we will use two ovarian cell lines in culture that have many of the features of the primary tumours including inhibin secretion. We will also use new techniques to scan over 500 genes involved in tumours in general to see whether we detect any unusual or distinctive patterns in this sub-group of tumours. A genome wide scanning technique will be used to seek changes in the DNA of the tumours, inparticular loss of genetic material or amplification of regions. Identification of the genetic changes within these tumours should enable better systems of classification, enhance prognostication and provide specific targets for the development of appropriate treatment strategies.Read moreRead less