Development Of Drug-loaded Antibody-targeted Nanoparticles To Kill Colorectal Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$513,146.00
Summary
COLORECTAL CANCER (CRC) is the most common cancer in the Western world. In Australia, the five-year survival rate after surgical resection of the primary lesion is 55%, and for patients with advanced disease the five-year survival rate is less than 10%. Colorectal cancer is relatively resistant to radiotherapy and chemotherapy and therefore there is great emphasis on identifying alternative modes of treatment. One approach that is attracting considerable attention is IMMUNOTHERAPY. In particular ....COLORECTAL CANCER (CRC) is the most common cancer in the Western world. In Australia, the five-year survival rate after surgical resection of the primary lesion is 55%, and for patients with advanced disease the five-year survival rate is less than 10%. Colorectal cancer is relatively resistant to radiotherapy and chemotherapy and therefore there is great emphasis on identifying alternative modes of treatment. One approach that is attracting considerable attention is IMMUNOTHERAPY. In particular, the A33 ANTIBODY system appears to have the potential to target colorectal cancer cells and achieve therapeutic outcomes. The A33 system has been well characterised in both a clinical and laboratory setting over the last few years and recent clinical trials with humanised versions of the A33 antibody have demonstrated rapid localisation and accumulation of radiolabelled A33 to colorectal cancer lesions. The application of NANOTECHNOLOGY to biological systems is likely to transform the way we treat a variety of diseases over the course of the next decade. Nanosized drug delivery vehicles have the potential to revolutionise the treatment of a number of diseases, cancer in particular. Hollow capsules can be synthesised with a drug sequestered inside the capsule, where the capsule wall performs a dual role of protecting the body from potentially harmful side effects of the drug, as well as protecting the drug from being degraded by the body. We plan to use these nanosized drug carriers, functionalised with the A33 antibody, to deliver chemotherapy agents directly to the colorectal cancer cells. We have recently demonstrated that in vitro, nanocapsules functionalised with the A33 antibody specifically bind to CRC cells, and once bound, the capsules are internalised. In this proposal we will test the ability of these particles to kill CRC cells in mice harbouring human tumours.Read moreRead less
Expression profiling of many cancers has revealed a common signature, including upregulation of SPARC and other extracellular matrix proteins (the SPARC cluster), which correlates with poor prognosis. This signature is similar to the wound healing gene expression profile after infection by the parasite, Leishmania. Moreover, genomic regions important for differences in the wound healing response in mice have been defined that may define novel genes important for regulating SPARC cluster gene exp ....Expression profiling of many cancers has revealed a common signature, including upregulation of SPARC and other extracellular matrix proteins (the SPARC cluster), which correlates with poor prognosis. This signature is similar to the wound healing gene expression profile after infection by the parasite, Leishmania. Moreover, genomic regions important for differences in the wound healing response in mice have been defined that may define novel genes important for regulating SPARC cluster gene expression. However, these regions contain 1000s of genes , and thus to define the critical genes other approaches are neccesary. The genetically manipulable animal model, Drosophila (vinegar fly), represents a ideal system to detect SPARC interacting genes that should help define the critical genes that regulate SPARC cluster genes. These regulators that trigger SPARC cluster gene expression are likely to define novel cancer causing genes.Read moreRead less
Molecular Markers Of The Progression Of Intestinal Metaplasia To Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$556,618.00
Summary
Gastric cancer (GC) is the second most common cause of cancer-related death globally. It is a surgically treatable disease that has good prognosis if detected at an early stage. The majority of patients in our community are detected at a late stage, where less than 20% of patients survive 5 years. The majority of GC is preceded by distinct histological stages that follow a progression from gastric mucosal inflammation, intestinal metaplasia (IM) and eventually cancer. These stages are characteri ....Gastric cancer (GC) is the second most common cause of cancer-related death globally. It is a surgically treatable disease that has good prognosis if detected at an early stage. The majority of patients in our community are detected at a late stage, where less than 20% of patients survive 5 years. The majority of GC is preceded by distinct histological stages that follow a progression from gastric mucosal inflammation, intestinal metaplasia (IM) and eventually cancer. These stages are characterised by genetic events that are largely unknown and occur over a period that can take years. It is also evident, especially in countries where GC is not as prevalent, that only a proportion of individuals will eventually develop GC. The long latency from the develpoment of IM and diagnosis of GC offers an opportunity to intervene and study the changes that lead to GC as well as find genes that may predict which individuals will progress. IM is the stage in which intervention is obvious. It is very easily diagnosed, is present for a long time and, for certain individuals, will eventually accumulate enough genetic events that will mandate progression to GC. Targeted screening of these individuals will enable a feasible strategy to find early GC, and avoid costly non-targeted screening. This proposal seeks to find key genetic events responsible for the transition of IM to GC. The first step utilises Affymetrix arrays to detect genes expressed in IM and specifically linked to GC. These candidates will be validated and used to study their role in the progression to GC using a mouse model of GC. This study is designed to find genes responsible for GC that can be used as: 1) a marker of progression in humans that will be used as a tool to stratify individuals into a screening protocol; 2) candidates to be tested in animal studies to study the pathogenesis of GC and potentially used as preventative or therapeutic targets.Read moreRead less
The Translocator Protein (TSPO) As A Novel Target For The Treatment Of Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$629,260.00
Summary
Alzheimer's disease (AD) is the most prevalent dementia, characterized by progressive loss of memory. An estimated 230,000 Australians currently suffer from AD, causing a huge impact on their families and carers, as well as on national finances. The present therapies are very limited, and there is no cure. Thus, there is a need for novel treatment strategies. We have developed novel drugs that represent an innovative approach to the treatment of AD.
Probing Developmental Causes Of Soft Tooth Enamel With Novel Mouse Models
Funder
National Health and Medical Research Council
Funding Amount
$470,112.00
Summary
Tooth decay is one of the most costly diseases in Australia and was recently called a national tragedy by the Prime Minister. The risk of decay increases if teeth don't harden properly in childhood. This project aims to clarify the causes of soft enamel and identify ways to prevent it. Two new test systems will be used to see how antibiotics and fluoride affect enamel hardening. Our findings will help the battle against tooth decay and guide the safe use of medicines in children.
Integrin Beta3 As A Therapeutic Target For Breast Cancer Metastasis To Bone
Funder
National Health and Medical Research Council
Funding Amount
$431,675.00
Summary
There are limited effective treatments for advanced breast cancer. The project investigates the role of a protein called integrin beta3 in the spread of breast tumours to bone, the most common site of secondary tumour formation (metastasis) in breast cancer patients. We will determine if the presence of integrin beta3 in breast tumours identifies patients at risk of developing bone metastases and test novel drugs against integrin beta3 in mice.