Improving The Efficacy Of Retinoid Therapy In Childhood Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$295,336.00
Summary
Cancer is still the commonest disease causing death in chilhood. Childhood neuroblastoma is a cancer of the nerve tissue which presents usually as a widely spread malignancy, which responds poorly to conventional therapy, indicating the need for novel treatment approaches. Vitamin A derivatives, or retinoids, given in addition to conventional therapy improves the cure rate for children with advanced neuroblastoma to 50%. We have shown that one likely mechanism of retinoid resistance is a deficie ....Cancer is still the commonest disease causing death in chilhood. Childhood neuroblastoma is a cancer of the nerve tissue which presents usually as a widely spread malignancy, which responds poorly to conventional therapy, indicating the need for novel treatment approaches. Vitamin A derivatives, or retinoids, given in addition to conventional therapy improves the cure rate for children with advanced neuroblastoma to 50%. We have shown that one likely mechanism of retinoid resistance is a deficiency of retinoic acid receptor beta, which is a necessary factor in the neuroblastoma cell for converting the retinoid anti-cancer signal into an irreversible cellular change. In this project we will define why some neuroblastoma cells express low levels of this protein and test new retinoid therapies.Read moreRead less
Improving The Treatment For Childhood Cancer: Neuroblastoma As A Model
Funder
National Health and Medical Research Council
Funding Amount
$5,029,092.00
Summary
One in three children with cancer still die of their disease, and side-effects of treatment are considerable. Over the past 15 years, the Chief Investigators have established themselves as a leading international research group in child cancer and have successfully applied their laboratory-based discoveries to improve the clinical management of children with malignant diseases. In particular, key advances have been made in basic cell biology, molecular biology and in defining clinically relevant ....One in three children with cancer still die of their disease, and side-effects of treatment are considerable. Over the past 15 years, the Chief Investigators have established themselves as a leading international research group in child cancer and have successfully applied their laboratory-based discoveries to improve the clinical management of children with malignant diseases. In particular, key advances have been made in basic cell biology, molecular biology and in defining clinically relevant molecular targets and prognostic indicators for the child cancer, neuroblastoma, the commonest solid tumour in young children. These findings have been made possible by the team assembling, over recent years, an extensive and unique range of in vitro and in vivo model systems, together with a large bank of clinical neuroblastoma specimens. In this research program, the team members propose an experimental approach that will continue their studies, focussing on cancer initiation and better target identification within cancer cells, leading to the development of effective and non-toxic novel compounds, possibly prevention strategies,and introduction of novel therapies into clinical trial.Read moreRead less
Novel Strategies For Improving Respiratory Support And Outcomes For Very Preterm Babies
Funder
National Health and Medical Research Council
Funding Amount
$8,381,820.00
Summary
Very premature birth is the commonest cause of illness and death in newborn babies, making it one of the most serious and costly issues in perinatal medicine. The major problem suffered by very premature babies is lung immaturity and its associated harmful effects on brain development. Most very premature babies require resuscitation followed by ventilatory support,often for several weeks. This is extremely expensive and places an enormous financial burden on health care systems. Furthermore, it ....Very premature birth is the commonest cause of illness and death in newborn babies, making it one of the most serious and costly issues in perinatal medicine. The major problem suffered by very premature babies is lung immaturity and its associated harmful effects on brain development. Most very premature babies require resuscitation followed by ventilatory support,often for several weeks. This is extremely expensive and places an enormous financial burden on health care systems. Furthermore, it increases the risks of respiratory illnesses, including bronchopulmonary dysplasia and chronic lung disease which can impair breathing and increase susceptibility to respiratory disease such as asthma later in life. The overall aim of this program is to improve outcomes for very premature babies, including less lung injury, better respiratory health and shorter stays in hospitals. In order to reduce the health burden caused by very premature birth on the community we need to know more about how it alters the normal development of the lungs in the newborn period and into later life. In particular, we need to understand the cellular and molecular processes involved in lung development so that we can identify gene networks and developmental processes that are disrupted by severe premature birth. Such knowledge is necessary to provide a more rational, scientific basis for managing and treating the alterations in lung structure and function caused by premature birth. We also need to develop better ways of resuscitating and ventilating these infants so that lung injury is minimized.The research team is led by two neonatologists and three biomedical research scientists with a proven record of effective collaboration. This team is internationally unique in that it includes practicing neonatologists, respiratory physiologists and molecular biologists who have collaborated together productively and are regarded as world leaders in their respective fields. New talents have been brought into the team to provide expertise in pulmonary stem cell biology, the design of novel steroid drugs, and clinical follow-up. Together, this team has the potential (a) to greatly enhance the understanding of the impact of very premature birth on the developing lung, (b) to improve resuscitation and ventilation techniques, and (c) to translate the new knowledge into clinical practice to improve the outcome for prematurely born babies. Using well characterized animal models we will determine gene networks involved in fetal lung development and how these are altered by premature birth. The successful transition from fetal to postnatal life is critical for survival at birth but more information is needed. Using newborn lambs and rabbits, we will trial novel strategies for enhancing the transformation of the immaturelung into an effective gas exchange organ at birth. New data on lung aeratioRead moreRead less
Next-generation Glioblastoma Multiforme Therapies Based On Multistage Delivery Nanovectors
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Nanomedicine provides novel therapies with enhanced treatment success and reduced side effects, which improve the patient’s quality of life. Drug delivery systems that are able to treat highly drug-resistant tumours such as glioblastoma multiforme (GBM) are a key target for nanomedicine-based therapies. We will investigate a new GBM treatment by developing a multistage delivery nanovector to selectively carry and release a combination of chemical and physical therapeutics.
Preclinical Development Of A Therapeutic Anticancer Antibody To C-Met
Funder
National Health and Medical Research Council
Funding Amount
$435,530.00
Summary
Many common cancers cannot be effectively treated. A range of these cancers (e.g. gastric and lung cancer) display the molecule c-Met on their cell surface. c-Met promotes tumour growth; therefore, blocking c-Met is a promising strategy for treating these cancers. However, no antibodies or drugs that target c-Met have been licensed. The therapeutics that are being developed to target c-Met all have considerable limitations. Thus, there is an opportunity to develop a 'best-in-class' therapeutic.
Therapeutic Targeting Of MYCN Oncoprotein Stability In Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$590,206.00
Summary
A high level of MYCN protein is a major indicator of aggressive neuroblastoma (NB) but unfortunately there have been many barriers to the design of targeted therapies. We have identified a protein called PA2G4 which is a cofactor for MYCN in promoting cancer cell growth. We have developed a compound which inhibits PA2G4 and MYCN protein levels and reduces tumour growth. We will examine how PA2G4 cause aggressive tumour characteristics and test new methods to block PA2G4.
Antibiotic Potentiators As An Alternative Therapeutic Option For The Treatment Of Extensively Drug-resistant Gram-negative Infections
Funder
National Health and Medical Research Council
Funding Amount
$856,858.00
Summary
Antibiotic mono-therapies are increasingly ineffective for hard-to-treat bacterial infections, forcing clinicians to rely on combinations of antibiotics. Our project has identified compounds that have weak to no antimicrobial potency in their own right, yet when combined with an existing antibiotic they potentiate its activity and restore its ability to treat resistant infections. These antibiotic potentiators are exciting alternatives to current therapies with reduced risk of induced resistance
Treatments that target cancer causing genes called oncogenes have resulted in new treatment paradigms for cancer. We suggest that outcomes of patients with cancer will be further substantially improved by understanding how cancers can overcome resistance to these treatments that develops in many patients. To accelerate the adoption of these and other new treatments for cancer we will also develop new frameworks for clinical trials.