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.
Design And Application Of New Nanomaterials Theranostic Platforms For Targeted Treatment Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$530,626.00
Summary
The project aims to develop intelligent drugs that attract to malignant tumors like magnets. These powerful, next-generation chemotherapy drugs seek out cancerous cells, allowing physicians to see exactly where tumours lie. Nanoparticles inside the drugs then switch on upon contact with X-ray radiation beams. This new method, which can diagnose, deliver targeted therapy and monitor the response to therapy all at the same time, would reduce the amount of radiation needed to kill cancer cells.
Developing Irreversible Electroporation Non-Thermal Tumor Ablation For Organ-Confined Prostate Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$290,512.00
Summary
IRE is technique for targeted tissue ablation. Electrodes placed into the targeted area deliver intense, brief electric pulses. Nano-scale pores are created in the cell membrane killing the cells but preserving the extracellular matrix. The pulses do not affect sensitive structures including neurovascular bundles, major vasculature and ductal systems preserving their function. It may address prostate regions implicated in prostate cancer without damaging vital structures, reducing side effects.
Cellular And Molecular Mechanisms Of Hedgehog Signaling In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$551,937.00
Summary
Breast cancer cells create the conditions for their own survival by communicating their needs to the healthy cells that surround them. We have previously shown that a molecule known as ‘hedgehog’ transmits biochemical signals between breast cancer cells and healthy cells. When hedgehog is ‘silenced’, tumours shrink and stop their spread. In this application, we will identify the cells receiving the hedgehog signal and identify how they support the growth and spread of breast cancers.
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.
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