Synthetic Lethality Screen Targeting A Defective Checkpoint In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$552,121.00
Summary
All cancers have defects in the mechanisms that regulate normal cell growth and division. These defects provide a growth advantage for the cancer, but can also be an Achilles Heel. In this project we will investigate targeting a defective control mechanism we found in a high proportion of melanomas. We will identify genes that when inhibited combine with the defective control to specifically kill tumour cells with this defect. Normal tissue is protected by its intact regulatory mechanism.
The critical role of the class III histone deacetylase SIRT2 in stabilizing N-Myc oncoprotein. Cancer is the commonest cause of death from disease in children. Neuroblastoma is the commonest solid tumor in early childhood. This project will investigate the critical roles of SIRT2 protein in increasing the expression of N-Myc oncoprotein and consequently inducing neuroblastoma, and SIRT2 inhibitors as anticancer agents.
Mitochondrially targeted anti-cancer drugs modulate the mitochondrial genome. Successful cancer management requires novel therapeutical approaches. This project will test the effect of a new class of compounds that target mitochondria, the powerhouse of the cells, where they suppress expression of mitochondrial genes. By this mechanism, cancers that are resistant to apoptosis induction can be inhibited.
Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen recepto ....Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen receptor (AR)-targeting therapies in human prostate tumours. The identification and functional assessment of these biomarkers will identify those that can be used as surrogate endpoints in clinical trials, facilitate earlier approval of investigational agents and lead to improved options for therapeutic management of prostate cancer.Read moreRead less
Fighting Epidermal Skin Cancers By Targeting Epidermal Clones That Accumulate Mutations
Funder
National Health and Medical Research Council
Funding Amount
$1,149,373.00
Summary
Common skin cancers such as basal and squamous cell carcinomas (BCC and SCC) are by far the most frequent cancer worldwide and require over a million interventions per year in Australia. This project will identify the skin cells that are most susceptible to give rise to cancer if excessively exposed to the sun and explores ways to prevent cancer formation. This will inform on new strategies to prevent new skin cancer development.
Strategies For Enhancing The Treatment Of Colon Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$590,785.00
Summary
Colorectal cancer is the third leading cause of cancer related death in Australia. Strategies to improve outcomes for these patients are urgently needed. This NHMRC SRF Fellowship will seek to identify new molecules in cancer cells which can be targeted to treat this disease, and to discover genes which can be used to improve patient response to treatment.
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.
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.
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.
Melanoma is the 4th most common cancer diagnosed in Australia. Advanced melanoma frequently spreads to other organs and can acquire resistance to anti-melanoma treatments, making it fundamentally incurable. I am focused on investigating the mechanisms underlying melanoma disease progression. I will achieve this by comparing the biological nature of melanoma cells at different stages of disease and therapy-resistance to identify new targets for the more effective treatment of patients with melano ....Melanoma is the 4th most common cancer diagnosed in Australia. Advanced melanoma frequently spreads to other organs and can acquire resistance to anti-melanoma treatments, making it fundamentally incurable. I am focused on investigating the mechanisms underlying melanoma disease progression. I will achieve this by comparing the biological nature of melanoma cells at different stages of disease and therapy-resistance to identify new targets for the more effective treatment of patients with melanoma.Read moreRead less