There is a need to improve early detection, monitoring of relapse, and treatments for melanoma, to increase long-term survival. My research vision is to use innovative and cutting edge approaches to conduct a range of complementary studies under three broad but inter-related themes: Theme 1 – Genetic predisposition to melanoma in the general population; Theme 2 – Genetic predisposition to melanoma in high-density families; Theme 3 – Somatic aberrations underlying melanoma development.
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.
Identifying Resistance Mechanisms Of Targeted BRAF Inhibitors In Metastatic Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$379,015.00
Summary
Late-stage melanoma is an aggressive skin cancer for which traditional treatment strategies such as chemotherapy are ineffective. Recently, a new class of targeted drugs (BRAF inhibitors) has become the standard of care for a subset of melanoma patients; however, long term treatment success is complicated by drug resistance. This study will identify the causes of resistance with the purpose to improve targeted drug strategies and increase survival rates for late-stage melanoma patients.
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.
Treatments that target cancer causing genes called oncogenes have resulted in new treatment paradigms for cancer. We suggest that outcomes of patients with cancer will be further substantially improved by understanding how cancers can overcome resistance to these treatments that develops in many patients. To accelerate the adoption of these and other new treatments for cancer we will also develop new frameworks for clinical trials.
Lung cancer is the commonest cause of cancer death worldwide. There is growing interest in the genetic causes of lung cancer. The overall aim of this research is to gain a better understanding of the steps in the genetic pathway of lung cancer spread. This knowledge is essential in the development of new targeted therapies and improvement in lung cancer prognosis.