Targeting A Master Regulator Of Tumour Cell Plasticity As A New Adjuvant Therapy For Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$780,338.00
Summary
Prostate cancer (PCa) claims the lives of over 3,000 Australian men each year. This highlights the urgent need to identify new molecular targets that can be developed as additional therapies for men with PCa. Our team has identified the protein, Zeb1, to be highly expressed in aggressive and treatment resistant forms of PCa. This study aims to characterise the role of Zeb1 in the lethal progression of PCa and to develop a new therapeutic agent to inhibit the production of ZEB1 by cancer cells.
Prostate cancer is the most common cancer in men, causing about 3,300 deaths per year. We have identified some small RNAs called microRNAs and other hormone regulators that can interfere with prostate cancer cell growth and signaling via the testosterone pathway. In this application we will be exploring the potential for each of these agents to reduce prostate cancer growth and the possibility that one or more could develop into a therapeutic target in the future.
Targeting MicroRNA-driven Mesenchymal To Epithelial Transition To Suppress Prostate Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$741,831.00
Summary
Prostate cancer kills ~3,000 men per year in Australia. The development of metastasis is the major cause of prostate cancer-associated death and has limited treatment options. In this study, we will characterise the role of a group of molecules, termed microRNAs, in prostate cancer metastasis. We will also test whether targeting microRNAs using novel drugs termed antagomiRs is an effective strategy to inhibit metastasis and thereby improve prostate cancer mortality.
Identification Of PACE-1 As A Novel Therapeutic Target For The Treatment Of Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$606,144.00
Summary
Advanced prostate cancer (PCa) remains the major therapeutic challenge since neither surgery nor systemic therapies are effective at this stage. Recently, we identified a protein called PACE-1 that is essential for PCa cell survival. We plan to investigate the roles of PACE-1 in the development and progression of prostate cancer. We will then test if PACE-1 inactivation alone or in combination with systemic cancer therapies will inhibit prostate tumor growth and disease progression.
Tailoring Targeted Therapy To DNA Repair-defective High-Grade Serous Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$802,247.00
Summary
Ovarian cancer is a major cause of cancer death in women because current treatments are inadequate. Half of aggressive ovarian cancers have abnormalities in DNA repair and should be susceptible to new PARP inhibitor therapy, yet not all those respond. By developing a new model of studying human ovarian cancers in mice, we can discover markers to predict which ovarian cancers will respond best to these exciting new treatments.
The Oligoadenylate-RNAseL Pathway May Provide A Specific And Low Toxicity Approach To Therapy For Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$439,314.00
Summary
We have discovered that a pathway used to fight viral infections can be triggered to produce massive cell death in the mammary gland. We hope to be able to trigger this response in breast cancers through the strategic combination of available drugs. If successful this project will establish a new therapeutic strategy for breast cancer.
Therapeutic Targeting Of The Colorectal Cancer Epigenome
Funder
National Health and Medical Research Council
Funding Amount
$537,045.00
Summary
Enhancer RNAs (eRNAs) are a new class of noncoding RNA molecules that have been linked to diverse functions that impinge on cancer, but their clinical relevance is unknown. Our work shows that distinct eRNAs are expressed in a subset of cancer and predict which cancer will respond to a cancer therapeutic agent called a BET inhibitor. Our proposal uses sophisticated preclinical models and cutting edge technology to investigate the functional role of enhancers and enhancer templated RNA in cancer.
We have identified genetic abnormalities in 5% of breast cancers that fall in a novel DNA element called BIME1. This proposal aims to determine whether these genetic abnormalities contribute to breast tumourigenesis and which genes and pathways are affected by these mutations. The outcomes of this proposal may lead to the development of novel therapies for breast cancer or could influence the choice of existing therapies for patients that harbour these genetic abnormalities.
Colorectal cancer (CRC) is one of the most common causes of cancer-associated death in the world. We aim to understand why some CRC patients stop responding to EGFR therapy. In particular, we will study small molecules called cytokines that are produced by the tumour microenvironment and determine if the inhibition of these cytokines can over-come the acquired resistance to therapy. Our goal is to identify new ways to improve the current treatment options for CRC patients.
EphA3 Is A Marker Of Glioma Stem/progenitor Cells And A Potential Target For Therapy.
Funder
National Health and Medical Research Council
Funding Amount
$585,860.00
Summary
EphA3 is a cell surface marker which is enriched on glioma ‘propagating’ stem cells (GSCs) and furthermore has a functional role in regulating GSC differentiation and fate determination. EphA3 therefore provides a novel therapeutic target for high-grade glioma.