Investigating Deregulation Of Mitosis As A Mechanism Of Tumourigenesis In MYCN-driven Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$372,298.00
Summary
Neuroblastoma chemotherapy often only works temporarily because a small number of tumour cells can resist drugs and eventually regrow as a new tumour. These resistant cells resemble the very first cells that turn into a cancer cell at tumour initiation. We have used single cell technology to uncover genetic markers of tumour initiating cells. In this project we will determine how these marker genes cause tumour initiation and develop therapies that target them in drug resistant neuroblastoma.
Optimising Targeted Polyamine Depletion For Treatment Of Childhood Neuroblastoma And Brain Tumours
Funder
National Health and Medical Research Council
Funding Amount
$928,152.00
Summary
Paediatric neuroblastoma and brain tumours, which often have dismal outcomes despite intensive therapy, have high levels of polyamines, which are essential for cell growth. We have shown that depleting polyamines, combined with chemotherapy, represents a highly promising therapy for neuroblastoma. We will make this exciting new treatment approach even more effective by comparing three ways of enhancing polyamine depletion, as a precursor to future neuroblastoma and brain tumour clinical trials.
Targeting The JNK-JUN Pathway To Overcome Therapy Resistance In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$694,729.00
Summary
Melanoma patients can display remarkable responses to targeted and immunotherapies. However most patients progress rapidly on targeted therapies and only a small proportion respond to immunotherapies. We have found that combination treatment with JNK inhibitors can overcome therapy resistance. We will determine the most efficacious JNK inhibitors available, and the optimal dosing and scheduling of combination treatment for evaluation in patients to improve responses, outcomes and survival.
Randomised Phase II Trial Of Neoadjuvant Chemotherapy +/- Concurrent Aromatase Inhibitor Endocrine Therapy To Down-stage Large Oestrogen Receptor Positive Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$2,302,496.00
Summary
Women diagnosed with large oestrogen receptor positive breast cancer are often treated with chemotherapy before surgery to reduce the size of the cancer, while treatment to lower oestrogen levels is given after surgery. This trial is studying if combining chemotherapy with oestrogen lowering treatment before surgery will better shrink the cancer which can improve the surgery options.
Overcoming Receptor Tyrosine Kinase Mediated Resistance To BRAF Inhibitors In Metastatic Melanoma, Colorectal And Lung Cancers.
Funder
National Health and Medical Research Council
Funding Amount
$574,958.00
Summary
The drug Vemurafenib results in good responses in melanoma patients. However, patients become resistant to treatment. We have identified specific receptors that can cause Vemurafenib resistance, which can be overcome by combination treatment with drugs to these receptors. We will assess melanoma patient samples for expression of these receptors which will be highly beneficial for selecting combination treatments to prevent drug resistance and ensure better prolonged outcomes.
High-Throughput Discovery Of Synergistic Drug Combinations For Metastatic Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,526,568.00
Summary
Treatment outcomes for patients with metastatic bowel cancer remain poor, with most tumours developing resistance within 24 months. A key problem is that cancers are genetically diverse, with some cells inevitably resistant to any given treatment. This study aims to discover effective drug combinations targeting distinct essential tumour cell functions through robotics-based pairwise testing of known drugs on bowel cancer cell lines representing the genetic diversity of the disease.
Novel Artemisinin-based Combination Therapies For Children Exposed To High Transmission Of Multiple Plasmodium Species
Funder
National Health and Medical Research Council
Funding Amount
$1,378,408.00
Summary
We recently found that the WHO-recommended combination antimalarial therapy artemether-lumefantrine and the candidate regimen dihydroartemisinin-piperaquine were not fully effective for both falciparum and vivax malaria in young PNG children, a group at risk of complications and death. We plan to study two new combinations (artesunate-pyronaridine and artemisinin-naphthoquine) and hypothesise that at least one will prove superior and be used as first-line treatment in PNG and similar countries.
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.
There is an unmet medical need to develop new therapies that are safer and potentially allow the treatment of a broader range of cancers. Inhibiting the immune checkpoints TIGIT and CD96 represents an opportunity that may parallel and indeed complement the activity and impact of other lymphocyte checkpoint inhibitors in human cancer (eg. PD1/PD-L1). While testing these as targets in mice we will also learn more about their ligand CD155 and their expression in human tumors.
Engineered Cell And Exosome Therapy For Pulmonary Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$838,490.00
Summary
Diseases affecting the blood vessels in the lungs cause early death and the currently available treatments are not curative. We will take advantage of the latest developments in the understanding of the molecular basis of these diseases to design and test a new treatment approach using cells and cell-derived products as a therapy.