AKR1C3 As A Potential Biomarker For Sensitivity Of T-lineage Acute Lymphoblastic Leukaemia To The Pre-prodrug PR-104
Funder
National Health and Medical Research Council
Funding Amount
$327,797.00
Summary
Multiagent chemotherapy is the most effective modality for the treatment of childhood ALL, the most common paediatric malignancy. Despite dramatic improvements in survival over the past 40 years, relapsed ALL remains one of the most common causes of death from disease in children. Therefore, innovative strategies are needed to benefit those children who respond poorly to established therapy. This application will test a novel therapy for a very aggressive subtype of childhood leukaemia.
Intraductal Carcinoma Of The Prostate: Indicator Of Aggressive Disease.
Funder
National Health and Medical Research Council
Funding Amount
$884,377.00
Summary
This proposal addresses the need to improve personalised treatment decisions for men with high risk familial prostate cancer as they have a very aggressive disease progression with a very poor clinical outcome. We will perform biological and pre-clinical studies to improve the clinical diagnosis, prognosis and treatment options for men with germline mutations in BRCA2 or BRCA1 genes who develop prostate cancer.
Deciphering Mechanisms Of Disease Evolution In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$845,093.00
Summary
In many patients, cancers are ever-changing, even after they have formed. This explains why many cancers can spread beyond the point of cure by surgery and why they can become resistant to treatments. This project will use patient melanomas and laboratory modelling to understand how melanomas change as they grow and spread. The results will be used to identify the nature of evolutionary changes in cancer in order to predict and even exploit them in treatment.
Pre-clinical Evaluation Of The LSD1 Inhibitor HCI-2509: Defining The Biomarkers Of Sensitivity And The Mechanisms Of Resistance
Funder
National Health and Medical Research Council
Funding Amount
$340,068.00
Summary
Despite aggressive multi-modal treatment strategies, limited progress in the treatment of Ewing sarcoma (paediatric bone malignancy), has been achieved over the past 30 years. As such, the advent of novel and targeted therapeutics with favourable efficacy/toxicity profiles are eagerly awaited. This proposal will investigate the therapeutic utility of LSD1 inhibition as a treatment for Ewing sarcoma and the underlying mechanisms of sensitivity/resistance to this unique agent.
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.
We recently discovered a new way to treat melanoma by inhibiting a protein called MDM4 that is important in promoting tumor growth in ~2/3 of melanomas. In this proposal, we will extend this work to see if anti-MDM4 therapy is effective in laboratory models that are more relevant to patients and in combination with other melanoma therapies. We will also explore additional ways of inhibiting MDM4 that may make anti-MDM4 therapy even more potent.
Identifying Castrate-resistant Tumour Cells In Localised Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$573,047.00
Summary
This proposal addresses one of the most important challenges in cancer: what cell population ‘drives’ tumour progression, and how can it be effectively targeted? We will define the prostate cancer cells that survive androgen withdrawal therapy and investigate new ways to target them. Eliminating these important cells earlier in disease progression will lead to increased survival for men with prostate cancer.
A Novel Protease And Growth Factor Regulated Signalling System In Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$856,743.00
Summary
Ovarian cancer is the leading cause of gynaecologic cancer death. Our project focuses on the role in ovarian cancer of a cellular receptor called CDCP1. We have previously shown that CDCP1 promotes growth and spread of ovarian tumours. Recently we have generated new data indicating that CDCP1’s activity is markedly increased by other proteins called proteases and growth factors. In this project we will define how these new pathways function, and if their blockade impedes ovarian cancer.
Novel Targeting Of Therapy-resistant Prostate Cancer Cells.
Funder
National Health and Medical Research Council
Funding Amount
$596,978.00
Summary
Prostate cancer is treated by removing male hormones (androgens). Although the bulk of the tumour regresses, some cells remain and the cancer often grows back in an aggressive form. We will study new ways to eliminate therapy resistant cancer cells and thereby provide more lasting treatments for prostate cancer. Ultimately, we hope to inform the design of ground-breaking clinical trials that could re-shape the treatment paradigm of advanced prostate cancer.
Elucidating The In Vivo Role Of The Pro-survival Gene Mcl-1 In Mammary Gland Development And Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$664,691.00
Summary
Breast cancer strikes one in 8 women by age 85 and is a major cause of morbidity and mortality. Despite recent improvements, the immense breast cancer burden demands new strategies that will radically improve patient outcomes. This project will address a hallmark of cancer: evasion of apoptosis. Understanding the molecular events that promote tumour survival and resistance to therapy represents a key area in cancer biology that has yet to be properly applied to breast cancer.