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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.
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.
Toll-like Receptor 2 Signalling As A Potential Therapeutic Target In Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$323,091.00
Summary
Stomach cancer is the fourth most deadly cancer in the world. Stomach cancer is closely linked with inflammation, and we have shown that a key inflammatory molecule, called toll-like receptor 2 (TLR2), can drive the development of stomach cancer. However, this occurs in a non-inflammatory manner. My research aims to understand how TLR2 is involved in the progression of stomach cancer, with the ultimate goal to find an early biomarker of disease, and to develop better therapies.
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.
Identification Of Interleukin-6 Trans-signalling As A Novel Target For Therapeutic Approaches To Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$627,089.00
Summary
Interleukin-6 (IL-6) has been implicated as a causative factor in lung cancer, the most lethal cancer worldwide, albeit by unknown mechanisms. Since IL-6 is also important for immune system homeostasis, the development of anti-IL-6 therapies requires an intimate knowledge of pathological versus physiological IL-6 signalling pathways. This project aims for the first time to define an alternative IL-6 signalling pathway, termed “trans signalling”, in the molecular pathogenesis of lung cancer.
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.