Antibody-based Inhibition Of ADAM10 As Cancer Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$652,788.00
Summary
Despite our advances in understanding the molecular basis of cancer, treatments for metastatic cancers are limited, emphasising an urgent need for strategies targeting several oncogenic pathways. We generated monoclonal antibodies effectively blocking the activity of ADAM10, an oncogenic cell surface protease that activates tumour growth, invasion and metastasis through multiple pathways. Here we describe the strategies that progress these antibodies as lead therapeutics for clinical testing.
EphA2 And EphA3 Maintain Tumour Initiating Cells And Are Therapeutic Targets In Brain Cancer
Funder
National Health and Medical Research Council
Funding Amount
$612,860.00
Summary
High-grade glioma (HGG) is the most common adult brain cancer; current treatments have increased survival times by months only. Our studies have shown brain cancer specific expression of a family of cell surface proteins called Eph receptors. Furthermore we have shown targeting these receptors with Eph antibodies leads to a significant reduction in brain cancer tumour growth. We now propose to test targeting these receptors in combination to achieve greater responses with minimal side effects.
EAR2: A Novel Driver Of Breast Cancer Proliferation
Funder
National Health and Medical Research Council
Funding Amount
$725,476.00
Summary
Drugs that block oestrogen are effective breast cancer treatments, but many patients are resistant to their effects. This research addresses a protein known as EAR2, that is elevated in breast cancer tissue compared to normal breast. We hypothesise that EAR2 drives breast cancer cell proliferation, and will test this using cell lines and mouse models. We will validate EAR2 as a new therapeutic target, benefitting patients underserved by current hormone therapies.
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.
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.
Novel Dual Domain Targeting Strategies Against ErbB Receptors
Funder
National Health and Medical Research Council
Funding Amount
$711,216.00
Summary
This project will develop innovative strategies to treat cancer through novel antibodies to erbB growth factor receptors, and identify ways to improve conventional treatments.
Nuclear Receptors And Triple Negative Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$681,979.00
Summary
This project will explore the potential for a nuclear receptor known as the thyroid receptor to suppress growth of breast cancer using cell culture models and mouse models. We hope to show that activating the thyroid receptors leads to a reduction in breast cancer growth providing evidence that the thyroid receptor pathway could be targeted for therapy.
Understanding Intrinsic And Acquired Resistance To Anti-FGFR Therapies
Funder
National Health and Medical Research Council
Funding Amount
$797,051.00
Summary
In vitro and in vivo preclinical data suggests that inhibition of FGFR in endometrial cancer patients may be a viable therapeutic approach. Data from other cancers suggests that despite remarkable initial responses to kinase inhibitors, cancer cells eventually develop resistance. This project aims to identify and characterize the mechanisms of resistance that emerge following FGFR inhibition in order to design combination therapies that may delay and/or prevent the emergence of resistance.
The Molecular Basis By Which IL-6 Family Cytokines And Pathogen Recognition Receptors Promote Inflammation-associated Stomach And Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
Lung and stomach cancer are the 2 most lethal cancers world-wide, and represent a growing number of cancers associated with chronic inflammation. However, the genes which trigger inflammation and then promote cancer in certain people remain largely unknown. Using mouse models for these inflammation-associated cancers, together with clinical specimens, our aim is to identify specific genes of the immune system which trigger chronic inflammatory responses that lead to cancer.
A new Src, PKCdelta and Akt regulated protease activated receptor system in metastasis. In contrast with localised cancer which can often be cured, curative treatment is generally not possible for cancer that has spread. This project will characterise a protein that drives the spread of cancer and to develop new approaches to treat patients at risk of developing these aggressive tumours that spread to other organs.