Advanced Anti-cancer Activities With Therapeutic Agents That Induce Tumor Cell Apoptosis And Antitumor Immune Responses.
Funder
National Health and Medical Research Council
Funding Amount
$85,701.00
Summary
The aim is to perform pre-clinical studies to identify new therapies for blood cancers. We will utilise three new anti-cancer agents that kill tumor cells and genetically engineered mice that develop cancer. We will determine if these three new agents kill the mouse tumor cells and activate anti-tumor immunity. The combined effect of killing blood cancer cells using new therapeutics, coupled with enhancing the anti-cancer immune response may hold the key to developing new treatments.
Analysis Of The Apoptotic And Therapeutic Effects Of Histone Deacetylase Inhibitors On Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$287,321.00
Summary
Multiple myeloma (MM) is an incurable progressive cancer of plasma cells within blood. It is the second most common blood cancer and represents 2% of all cancer-related deaths. Statistics show increasing incidence and decreasing age of onset. The cause and progression of MM is poorly understood and current treatments are frequently followed by relapse. This project will assess exciting new therapies against the survival of MM cells leading to more effective treatments in the future.
Investigating Tumour Biology Using Regulated RNAi In Cells And Mice
Funder
National Health and Medical Research Council
Funding Amount
$305,915.00
Summary
Inhibiting gene expression using the recently discovered process known as RNA interference (RNAi) can be used as an experimental tool to analyse specific genes, in cells and genetically engineered animal models of human disease. I propose to use RNAi to mimic human cancer gene mutations in mouse cancer models, and aim to discover novel tumour suppressor genes. A further aim is to validate potential drug targets in cancer by using RNAi to inhibit specific genes in established mouse tumours.
Analysis Of Apoptotic Pathways To Develop Better Therapies For Unresponsive Cancers.
Funder
National Health and Medical Research Council
Funding Amount
$130,807.00
Summary
Tight control of the balance between cellular survival and death is important for normal development and to avoid numerous diseases. Inappropriate survival of precancerous cells can contribute to oncogenesis. Anti-cancer therapies act by inducing a cellular self-destruct program in tumour cells, and blocks in pathways controlling this process can lead to resistance to anti-cancer treatments. Defining cell death pathways will enable the development of better therapies for incurable cancers.
Function Of FOR Gene Products In Normal And Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$521,310.00
Summary
Cancer cells usually exhibit the loss of control of normal cell functions. This involves the increase of proteins which promote growth and cell division and the decrease in proteins which inhibit growth and cell division. Loss of function may also occur in proteins that are normally involved in killing the cell when growth becomes uncontrolled. Many of these proteins interact with one another and in so doing establish pathways and networks of control which must be perturbed and overridden in the ....Cancer cells usually exhibit the loss of control of normal cell functions. This involves the increase of proteins which promote growth and cell division and the decrease in proteins which inhibit growth and cell division. Loss of function may also occur in proteins that are normally involved in killing the cell when growth becomes uncontrolled. Many of these proteins interact with one another and in so doing establish pathways and networks of control which must be perturbed and overridden in the cancer cell. Sometimes this is because the role of the protein is altered in the cancer cell compared to what it normally is in a normal cell. The main aim of this study is to understand the role that is played by a set of proteins that are coded by a single gene. This gene (which we refer to as the FOR gene) spans a region of the human genome which is sensitive to a particular type of mutation. This mutation takes place early in tumour development and therefore we believe that it has important role to play in determining the fate of the cell - helping to cause it to become a tumour cell. We will find out which other proteins in the cell the FOR proteins interact with. Where these proteins are known then this will help determine the pathways in the cell in which the FOR proteins participate. In another approach we will establish animal models (in mice and flies) of mutations in the FOR genes of these species. The transgenic mice will help us find out whether the mutations that we have observed in the FOR gene in various human cancers cause increased sensitivity to mutagens and in so doing aid in transforming normal cells into cancer cells. The transgenic flies will help us identify the metabolic pathways in which the FOR proteins participate. These studies will help understand the roles of the FOR proteins and their significance in cancer.Read moreRead less
Defining The Apoptotic And Therapeutic Activities Of Histone Deacetylase Inhibitors.
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
HDAC inhibitors (HDACi) are new chemotherapeutic drugs that kill tumors cells through a cell suicide process called apoptosis. We have now established a mouse model of human lymphoma whereby pro-apoptotic proteins have been eliminated or anti-apoptotic proteins overexpressed. We will identify the apoptotic proteins and pathways that are necessary for HDACi to kill cancer cells. Such information will lead to a more targeted or rational approach to chemotherapy using HDACi.
Mechanisms Of Glucocorticoid Resistance In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Glucocorticoids are extremely active drugs used in the treatment of childhood acute lymphoblastic leukaemia (ALL), yet a proportion of patients respond poorly to therapy and exhibit resistance at relapse. Clinically relevant mechanisms of glucocorticoid resistance are poorly understood, principally due to lack of appropriate experimental models. This project will reveal novel mechanisms of drug resistance in childhood leukaemia and lead to novel therapeutic strategies to improve outcome.
Analysis Of CD95L And TRAIL Apoptotic Pathways In Glioma.
Funder
National Health and Medical Research Council
Funding Amount
$423,055.00
Summary
Most patients with the brain cancer malignant glioma die within two years of diagnosis, thus innovative approaches to treatment are desperately needed. Mutations which prevent the precancerous cells from responding to suicide (apoptotic) signals can contribute to tumourigenesis. As standard treatment regimes act by inducing this cellular suicide machinery, tumour cells with apoptotic pathway alterations can be resistant to conventional therapies. Malignant gliomas are typically resistant to chem ....Most patients with the brain cancer malignant glioma die within two years of diagnosis, thus innovative approaches to treatment are desperately needed. Mutations which prevent the precancerous cells from responding to suicide (apoptotic) signals can contribute to tumourigenesis. As standard treatment regimes act by inducing this cellular suicide machinery, tumour cells with apoptotic pathway alterations can be resistant to conventional therapies. Malignant gliomas are typically resistant to chemo- and radiotherapy, and therefore may have altered apoptotic pathways. By identifying the components of apoptotic pathways in glioma cells, rational design of either novel drugs, or treatments which will restore-enable susceptibility of the tumour cells to currently available therapies will be feasible. Here we will focus on the suicide pathways triggered by the molecules CD95L and TRAIL. We will characterise the sensitivity of glioma cells to CD95L and TRAIL, chemotherapeutic drugs and irradiation. We will then systematically survey the molecules implicated in CD95L and TRAIL-mediated cell death, based on studies in other cell types, to determine the relevant components of the molecular pathways which lead to apoptosis following CD95L-TRAIL exposure. We will also assess the roles played by known inhibitors, in determining resistance to CD95L and-or TRAIL, and will perform screens for novel inhibitors of these pathways. This study will elucidate the molecules responsible for the CD95L-TRAIL-mediated apoptosis seen in some glioma cells, and the molecules which confer resistance to these treatments in others. We will also learn whether the typical resistance to chemo- and radiotherapy observed in gliomas is mechanistically linked to resistance to CD95 and-or TRAIL resistance. This knowledge will be valuable for the rational design of diagnostic and therapeutic agents for glioma, and potentially for other diseases.Read moreRead less
THE ROLE OF SMALL NON CODING RNAS IN BONE MARROW MEDIATED TUMOR ANGIOGENESIS. Despite advances in treatment and diagnosis cancer remains the leading underlying cause of deaths, representing about a third of all deaths each year in Australia (ABS stats. www.abs.gov.au). The ability to understand the process of tumour vascularisation and spread has enormous economic and social outcomes. Indeed, the most effective anti-angiogenic therapy developed to date Avastin (aka Bevacizumab), although providi ....THE ROLE OF SMALL NON CODING RNAS IN BONE MARROW MEDIATED TUMOR ANGIOGENESIS. Despite advances in treatment and diagnosis cancer remains the leading underlying cause of deaths, representing about a third of all deaths each year in Australia (ABS stats. www.abs.gov.au). The ability to understand the process of tumour vascularisation and spread has enormous economic and social outcomes. Indeed, the most effective anti-angiogenic therapy developed to date Avastin (aka Bevacizumab), although providing only a modest survival advantage (4-6 months) has annual sales of several billion dollars. microRNA represent a relatively newly discovered form of gene activity regulation. Taking a key leadership role in this area will put Australian science at the forefront of international research initiatives.Read moreRead less