Molecular Subtype Specific Therapy In High Grade Serous Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$832,254.00
Summary
High grade serous ovarian cancer (HGSC) is the most common type of ovarian cancer, accounting for about two thirds of all deaths from the disease.Several years ago we identified distinct subtypes of HGSC (C1, C2, C4, C5) based on patterns of gene activity. We found that women with the C5 subtype generally had poor survival, and we mapped genes that were specifically active in C5 tumours. In this application we aim to develop therapies that are specifically targeted to the C5 HGSC.
Development Of Follistatin As Novel Cancer Therapeutic
Funder
National Health and Medical Research Council
Funding Amount
$494,324.00
Summary
In this project, we aim to rapidly commercialise our discovery that Follistatin, an endogenous hormone, can dramatically improve the efficacy of platinum-based chemotherapy in lung cancer.
Anti-metastasis Therapy Via Nanoparticle Mediated Drug Delivery
Funder
National Health and Medical Research Council
Funding Amount
$835,199.00
Summary
Most cancer deaths are caused by tumours that have spread to other vital organs, a process called metastasis. The common treatment for metastatic disease is chemotherapy, but the amount given is limited by toxicity to the patient. In this project, we are developing a way of delivering the therapies only to tumour cells, thereby sparing normal tissues. We are using nanoparticles that have a molecule on their surface that directs the therapy directly to tumour cells.
A Randomized Trial Of 2 Radiation And Systemic Therapy Strategies In Good Prognosis Advanced Human Papilloma Virus -associated Cancer Of The Tonsil And Base Of Tongue
Funder
National Health and Medical Research Council
Funding Amount
$1,097,932.00
Summary
Cancers of the tonsil and base of tongue due to the human papilloma virus have a better prognosis than other head and neck cancers, but standard treatment can result in significant acute and late side effects. This trial aims to compare two types of chemotherapy and radiotherapy that are less intensive than standard treatment. The aim of the trial is to determine which treatment is associated with better quality of life and less side effects, while maintaining efficacy.
Strategies For Enhancing The Treatment Of Colon Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$590,785.00
Summary
Colorectal cancer is the third leading cause of cancer related death in Australia. Strategies to improve outcomes for these patients are urgently needed. This NHMRC SRF Fellowship will seek to identify new molecules in cancer cells which can be targeted to treat this disease, and to discover genes which can be used to improve patient response to treatment.
Therapeutic Targeting Of Precancerous Stem Cells In T Cell Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$674,737.00
Summary
We have recently identified a stem cell population causes T cell leukaemia. These cells may also survive conventional leukaemia therapies and cause relapse. This project will determine whether these stem cells can be killed using conventional leukaemia therapeutics. In addition, we will identify new therapeutic targets to eliminate these cells. This will enable us to specifically target the cells responsible for leukaemia relapse.
RECOMBINANT MALARIAL PYRIMIDINE ENZYMES AS DRUG TARGETS
Funder
National Health and Medical Research Council
Funding Amount
$229,750.00
Summary
Malarial parasites have now developed resistance to most of the available drugs and there is an urgent need for drugs with new mechanisms of action. Institutions collaborating on the Malarial Genome Project have sequenced the majority of DNA in the 14 chromosomes. The nucleotide sequence available on the internet contains thousands of open reading frames (ORFs) which encode proteins essential for survival of the parasite. Many of these proteins are enzymes which are suitable targets for drug dev ....Malarial parasites have now developed resistance to most of the available drugs and there is an urgent need for drugs with new mechanisms of action. Institutions collaborating on the Malarial Genome Project have sequenced the majority of DNA in the 14 chromosomes. The nucleotide sequence available on the internet contains thousands of open reading frames (ORFs) which encode proteins essential for survival of the parasite. Many of these proteins are enzymes which are suitable targets for drug development. A knowledge of the molecular architecture of the active site of such enzymes provides a template for drug design. The malarial parasite, Plasmodium falciparum, can only synthesise pyrimidine nucleotides for DNA via the de novo pyrimidine pathway. We have cloned the genes encoding three of the enzymes of the de novo pathway using sequence information from the Malarial Genome Project. Dihydroorotase, orotate phosphoribosyltransferase, and OMP decarboxylase, catalyse reactions 3, 5 and 6 of the pathway. We have expressed these enzymes in the bacterium Escherichia coli enabling large-scale production of these drug targets. We propose to characterise the catalytic and inhibitory properties of these enzymes, and grow protein crystals for determination of atomic structures by x-ray diffraction. The structures will provide templates for rational design of new antimalarial drugs. In a second approach for develoment of new drugs, the 3 malarial enzymes will be screened against chemical libraries for inhibition of catalytic activity. The initial screen will utilise a high throughput Biacore 3000 instrument which detects strong interactions between a target enzyme and candidate inhibitors. A thorough knowledge of the catalytic mechanisms, the three-dimensional structures and novel first generation inhibitors of these 3 malarial target enzymes, will provide a strong basis for development of new antimalarial drugs.Read moreRead less
Genetic And Epigenetic Mechanisms Determining Responses To Therapies In Non-small Cell Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$22,677.00
Summary
Lung cancer results in more cancer related deaths than any other cancer. The aim of this study is to identify prognostic and predictive markers for patients with non-small cell lung cancer (NSCLC) treated with chemotherapy, palliative radiotherapy and also novel targeted agents. This will help to better utilise these treatments and hopefully improve outcomes in patients with NSCLC.
I am a cancer molecular and cell biologist determining the mechanisms of anticancer drug action and resistance in both childhood and adult malignancies. My research involves the development and investigation of both in vivo and in vitro models of resistan
Identifying The Molecular Mechanisms Of Synergistic And Antagonistic Drug-drug Interactions In Combination Chemotherapies
Funder
National Health and Medical Research Council
Funding Amount
$412,685.00
Summary
Drug combinations in chemotherapy hold promise for more effective treatments and for overcoming drug resistance, but the search for effective combinations is challenging. The combination therapy R-CHOP is often curative for Diffuse Large B-cell Lymphoma (DLBCL). Both cellular drug interactions and evolutionary drug interactions will be quantified in DLBCL cells, to understand the defining features of effective combinations and guide the future rational design of combinations.