A Novel Mechanism For Sustained Proliferation Of Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$565,881.00
Summary
We have found that some tumours use a previously unknown strategy for evading the normal limits on cellular proliferation. We will analyse the molecular details of this mechanism in order to (i) understand how it works, (ii) devise a diagnostic test, and (iii) lay the foundations for developing treatments that specifically target this type of cancer.
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.
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.
More Effective Therapeutic Targeting Of High Risk Childhood Cancer: Neuroblastoma As A Model
Funder
National Health and Medical Research Council
Funding Amount
$6,601,220.00
Summary
Cancer is the commonest cause of death from disease in Australian children. Childhood neuroblastoma is a particularly aggressive cancer, for which new treatment approaches are urgently needed. The team aims to discover better safer therapies for children with this cancer, conducting clinical trials using new drugs and novel drug combinations. We will also investigate novel ways of targeting neuroblastoma cells and identify therapeutic targets in neuroblastoma-initiating cells.
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.
Targeted Inhibition Of The FACT (Facilitates Chromatin Transcription) Complex As A Novel Therapeutic Approach In Aggressive Childhood Cancers
Funder
National Health and Medical Research Council
Funding Amount
$1,029,488.00
Summary
Our research focusses on the most aggressive of all childhood cancers, and our aim is to develop novel therapies for these malignancies. We have discovered a new drug target called "FACT" in aggressive brain and solid tumours of childhood. Targeting FACT with a new class of drugs termed "curaxins" has a powerful anti-tumour effect. We aim to investigate the potential of these drugs as a new, effective therapy for incurable childhood cancers.
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.
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 Novel Molecular Target Capable Of Abrogating Neuroblastoma Development
Funder
National Health and Medical Research Council
Funding Amount
$802,499.00
Summary
Although modern chemotherapy has significantly improved survival rates for many childhood cancers, the outlook remains dismal for children with advanced staged neuroblastoma. These patients frequently have alterations in the cancer-causing gene called MYCN. Using pre-clinical models of MYCN-driven neuroblastoma and genome sequencing we have discovered a gene that can completely block the action of MYCN and prevent neuroblastoma growth. This work will characterize the function of this novel gene.