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.
Significance Of Soluble PD-L1 In Melanoma Patients
Funder
National Health and Medical Research Council
Funding Amount
$561,236.00
Summary
A class of new immunotherapy drugs called “antibodies of immune checkpoints” can lead to long-lasting melanoma regression, but they are only beneficial to a subset of patients. This project will potentially identify the increased expression of a protein called PD-L1 in the blood as a biomarker predictive of responses of melanoma patients to these new drugs. The results will be instructive for selection of patients for the treatment.
Towards Better Treatments For Acral Melanoma Through Functional Genomics
Funder
National Health and Medical Research Council
Funding Amount
$1,456,823.00
Summary
Acral melanoma is an uncommon melanoma subtype with bad prognosis that has been poorly characterised at the molecular level. The project will conduct comprehensive analysis of acral melanoma at the DNA, RNA and protein levels. Through subsequent functional follow-up studies of key drivers of this cancer type we will identify novel drug targets to treat this disease.
Molecular Subtype Specific Therapy In High Grade Serous Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$832,254.00
Summary
High grade serous ovarian cancer (HGSC) is the most common type of ovarian cancer, accounting for about two thirds of all deaths from the disease.Several years ago we identified distinct subtypes of HGSC (C1, C2, C4, C5) based on patterns of gene activity. We found that women with the C5 subtype generally had poor survival, and we mapped genes that were specifically active in C5 tumours. In this application we aim to develop therapies that are specifically targeted to the C5 HGSC.
The exciting field of small RNA research was the subject of the 2006 Nobel Prize in Medicine, and holds great potential in the diagnosis and prognosis of disease such as cancer. Recent clinical studies suggest that drugs inhibiting small RNAs called microRNA present novel therapeutic opportunities. By defining the non-specific effects of such drugs and investigating new avenues for their delivery, this project will secure the safe application of these drugs into the clinic.
MPO-ANCA GN is a major cause of renal failure. Current treatments are toxic and poorly effective. Excessive DNA production resulting in prominent deposits of extracellular DNA are seen in glomeruli of patients with MPO-ANCA GN. This study will look at the pathological role of DNA and in a relevant animal model, use DNase I treatment to dissolve deposited DNA and treat anti-MPO autoimmunity and GN. This evidence will allow the introduction of DNase I in clinical trials.
The FGFR Family As Drivers And Biomarkers Of Regorafenib Response In Gastric Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$670,784.00
Summary
The drug regorafenib has recently emerged as a potential new treatment for patients with gastric (stomach) cancer. We have discovered that gastric cancer cell lines which express high levels of members of the FGFR family are highly sensitive to this drug. This project will define the potential of targeting the FGFR family in gastric cancer,the value of FGFR1-4 as markers of regorafenib response, and develop strategies for enhancing regorafenib activity in this difficult to treat disease.
Modelling BET Inhibitor Resistance In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$764,796.00
Summary
Mutations in epigenetic regulators in AML not only imply a causative role for these proteins in AML but also provide potential targets for therapeutic intervention. One of the most promising epigenetic therapies to have emerged in the last decade are small molecule inhibitors targeted to the Bromodomain and Extra Terminal (BET) family of proteins. This proposal will elucidate the cellular and molecular mechanisms that drive resistance to this new class of drugs
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.
Melanotransferrin: A “Missing Link” And A Novel Pharmacological Target For Treatment
Funder
National Health and Medical Research Council
Funding Amount
$613,848.00
Summary
Despite >30 years of research, the precise function of the protein, melanotransferrin (MTf), is unknown. However, we have breakthrough evidence that MTf stimulates WNT signalling as a major driver in cancer progression. We will investigate this hypothesis, which will underpin new cancer therapies. Indeed, we designed a new class of drugs that target the WNT pathway via up-regulating the WNT inhibitor, NDRG1. This drug (DpC) inhibits MTf expression to block tumour cell growth and metastasis.