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Targeting Histone Deacetylases To Overcome Resistance Of BRAFV600E Melanoma Cells To Apoptosis
Funder
National Health and Medical Research Council
Funding Amount
$353,140.00
Summary
Results from early clinical studies with a new class of drugs in the treatment of melanoma have been very encouraging, but most tumors initially respond to the drugs regrow after short periods. We have recently shown that this is mainly related to resistance of melanoma cells to cell death induced by the drugs. In this project, we aim to explore a novel approach to overcome this resistance. If successful, the results will lead to new approaches in the treatment of melanoma.
Development Of Antimalarial Histone Deacetylase Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$573,676.00
Summary
Human histone deacetylases (HDACs) are enzymes clinically validated as targets for cancer chemotherapy. Different HDAC enzymes are important for survival of infectious organisms, such as protozoan Plasmodium parasites that cause malaria. This project will develop promising drug leads that kill the parasites without damaging human cells through preclinical studies in mice towards a future clinical trial for the treatment of malaria in humans.
The Distinctive Roles Of Tissue Transglutaminase Isoforms In Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$311,567.00
Summary
Neuroblastoma is the commonest solid tumour in early childhood. Neuroblastoma caused by N-Myc oncogene accounts for about one third of the disease and represents a more aggressive subtype with a worse clinical outcome. This project aims to identify factors responsible for N-Myc-induced neuroblastoma initiation and factors sensitizing neuroblastoma cells to anti-cancer drugs, and to provide the basis for clinical trials of a combination therapy in children with neuroblastoma.
Histone Deacetylase Inhibitors (HDIs) With Antineoplastic And Antiosteolytic Properties
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Metastatic bone disease is very common in patients with many forms of solid tumours. Our approach to use Histone Deacetylase Inhibitors (HDIs), to target bone metastases offers an exciting therapeutic potential. Treatment with HDIs will have the potential to suppress cancer-induced bone destruction by integrating the cytotoxic and osteotropic properties that reside within the same compound. Our preclinical data will facilitate the translation of HDIs to clinical trials for bone cancer.
Targeting Histone Deacetylases For The Therapy Of Myc-induced Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$356,513.00
Summary
Neuroblastoma is the commonest solid tumour in early childhood. Pancreatic cancer is the fourth leading cause of cancer death in adults. In this application, we will define how proteins called histone deacetylases promote cancer initiation and progression, and whether combination therapy with an inhibitor of the histone deacetylases and another anti-cancer agent exert efficient synergistic anti-cancer effects in animal models of neuroblastoma and pancreatic cancer.
Targeting The Histone Methyltransferase DOT1L For The Therapy Of Myc-induced Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$356,127.00
Summary
Neuroblastoma is the commonest solid tumour in early childhood. Pancreatic cancer is the fourth leading cause of cancer death in adults. In this application, we will define how a protein called histone methyltransferase DOT1L promotes cancer initiation and progression, and whether inhibitors of the histone methyltransferase DOT1L exert efficient anti-cancer effects against neuroblastoma and pancreatic cancer.
A Phase II Study Of Continuous, Low-dose LBH 589 (Panobinostat) In Patients With Refractory Solid Tumors, Including CNS Tumors
Funder
National Health and Medical Research Council
Funding Amount
$811,512.00
Summary
Research done recently across three separate Australian laboratories has shown great promise with a new anti-cancer drug LBH589 used for cancers in children and young adults. We wish to start a clinical trial of LBH589 in children and young adult patients with cancer.
Targeting The Class IIa Histone Deacetylases In Metabolic Disease
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
Dysfunctional metabolism in skeletal muscle is integral in the development of metabolic diseases, such as obesity and type 2 diabetes. This project will examine proteins that alter the way genes are expressed for their role in dysfunctional metabolism in muscle. This project could uncover new therapies for the treatment of metabolic diseases.