Characterisation Of Two Novel Markers Of Osteosarcoma Metastasis As Potential Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$624,500.00
Summary
Osteosarcoma (OS) is the most common bone tumour in children and adolescents. In spite of aggressive chemotherapy, OS tumours that metastasise to the lungs result in dismal long-term survivals of only 10-20%. For these patients, new treatment options are desperately needed. In this proposal we show compelling data identifying two new markers of OS metastasis. This research aims to validate the suitability of these novel markers as therapeutic targets to prevent OS metastasis.
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.
Peritoneal Metastases From Colorectal Carcinoma: Exploring The Potential Of Immunotherapy As A Treatment Adjunct
Funder
National Health and Medical Research Council
Funding Amount
$89,197.00
Summary
Twenty percent of patients with bowel cancer have disease involving the lining of the abdomen, called the peritoneum. These patients do poorly. The majority are inoperable, and chemotherapy has poor response in these patients. Therefore, there is a dire need to explore new treatments. Newer drugs that stimulate the immune cells to fight cancer have shown promise in other cancers. We aim to assess the potential of this treatment in peritoneal disease, with the aim of improving patient outcomes.
Pharmacological Development Of Synthetic Analogues Of Cytochrome P450-mediated Omega-3 Fatty Acid Epoxides As Novel Anti-metastatic Agents
Funder
National Health and Medical Research Council
Funding Amount
$865,174.00
Summary
Dietary ?-3 and ?-6 fatty acids respectively decrease and increase the risk of cancer spread, or metastasis. We have found that ?-3 fatty acid epoxide metabolites inhibit the growth and migration of tumour cells. We have prepared derivatives of these ?-3 epoxides that retain anti-cancer properties in cells. In this project we will develop analogues of these ?-3 epoxides that are suitable for in vivo testing in animal models of breast cancer metastasis as a new class of potential anti-metastatic ....Dietary ?-3 and ?-6 fatty acids respectively decrease and increase the risk of cancer spread, or metastasis. We have found that ?-3 fatty acid epoxide metabolites inhibit the growth and migration of tumour cells. We have prepared derivatives of these ?-3 epoxides that retain anti-cancer properties in cells. In this project we will develop analogues of these ?-3 epoxides that are suitable for in vivo testing in animal models of breast cancer metastasis as a new class of potential anti-metastatic drugs.Read moreRead less
Identification Of New Therapeutic Targets In Neuroblastoma Through ABCC Transporter Associated Pathways.
Funder
National Health and Medical Research Council
Funding Amount
$591,436.00
Summary
Neuroblastoma accounts for 15% of childhood cancer deaths. Children diagnosed over 1 year have survival rates below 40%. New research shows that certain genes previously implicated in drug resistance contribute to neuroblastoma development. We will investigate their role using a new neuroblastoma model and a range of biochemical and cell biology techniques. This research will improve our understanding of neuroblastoma biology and identify new therapeutic targets in this and other cancers.
We have found that leptin, a new hormone produced by fat cells which regulates appetite and metabolism, is a powerful inhibitor of osteoclast formation. Osteoclasts are large cells present in bone which are responsible for bone resorption and therefore these cells contribute to common bone conditions such as osteoporosis, Paget's disease and bone cancer. Osteoporosis causes a great deal of pain and disability and it alone costs the Australian taxpayers more than $400 million per year. Persons wh ....We have found that leptin, a new hormone produced by fat cells which regulates appetite and metabolism, is a powerful inhibitor of osteoclast formation. Osteoclasts are large cells present in bone which are responsible for bone resorption and therefore these cells contribute to common bone conditions such as osteoporosis, Paget's disease and bone cancer. Osteoporosis causes a great deal of pain and disability and it alone costs the Australian taxpayers more than $400 million per year. Persons who are overweight tend to have higher circulating blood levels of leptin and also tend to have denser bones, which suggests that there might be a relationship between blood leptin and bone density or strength. Furthermore, leptin is produced in the bone marrow which is where osteoclasts are produced. Osteoclasts are formed from white blood cells which are present in the bone marrow and the blood. Very recent discoveries have identified a family of new factors which play a key role in the formation of osteoclasts. One of these factors has been called osteoprotegerin and is an inhibitor of osteoclast formation. Mutant mice lacking osteoprotegerin have greatly increased numbers of osteoclasts and severe osteoporosis whereas mutants with too much osteoprotegerin have bones which are much denser than normal. The availability of these factors now allows the generation of human osteoclasts in the laboratory which enables the further study of how the process is regulated. We have found that leptin increases the amount of osteoprotegerin produced by white blood cells and we believe that this is the major way that leptin inhibits osteoclast generation. In this project, we intend to further investigate how and why leptin is able to influence the generation and function of osteoclasts as leptin may be a suitable treatment for osteoporosis and other bone diseases.Read moreRead less
The Mechansim Of Cachexia Induced By The TGF-b Superfamily Cytokine, MIC-1
Funder
National Health and Medical Research Council
Funding Amount
$544,200.00
Summary
MIC-1 is a protein first cloned and characterised by our research group. It belongs to the TGF beta protein superfamily which is very important in development of cancer, wound - fracture healing and inflammation. Recent evidence also suggests it can act as an appetite suppressant, and this is especially relevant in conditons like cancer where it is overproduced. This project seeks to understand the mechanisms for its capacity to modify appetite
Using MiR-200 To Find New Therapeutic Targets For Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$563,152.00
Summary
Neuroblastoma is one of the most common cancers in children. We have found that a genetic regulator, called microRNA, can limit the ability of neuroblastoma cells to invade surrounding tissues and metastasise. We aim use the microRNAs to find new therapeutic targets that may work in combination with existing treatments, reducing the short term toxicity and long term deleterious effects of current treatments.
Treating Metastatic Melanoma With Stereotactic Ablative Body Radiotherapy And IMmune Pathway ACTivation (SABR-IMPACT)
Funder
National Health and Medical Research Council
Funding Amount
$185,445.00
Summary
Metastatic melanoma has historically had extremely poor survival. Drugs that activate the immune system provide some hope, and in the minority who respond survival beyond 10 years is possible. Radiotherapy causes local tumour death resulting in antigen exposure and systemic effects that may also stimulate the immune system. The combination of radiotherapy and immune activating drugs may be synergistic and result in improved survival for a greater proportion of patients.
Early Detection Of Melanoma Metastases Using MicroRNA As Novel Biomarkers
Funder
National Health and Medical Research Council
Funding Amount
$109,363.00
Summary
The use of a minimally invasive blood test to measure the circulating levels of melanoma-specific miRNAs may provide a rapid assessment for clinical management of the disease during dissemination of the tumour. This work has the potential to provide new prognostic markers for melanoma as well as to identify new gene targets for the design of rational therapies to treat this disease.