Targeting Microtubules To Overcome Chemoresistance In Pancreatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$594,336.00
Summary
Pancreatic cancer is a devastating disease with a dismal prognosis because it is extremely resistant to chemotherapy agents. We plan to examine the expression of proteins called microtubules in pancreatic cancer and assess their role in drug resistance. It is anticipated that the findings of these studies will lead to the development of effective approaches to sensitise the cancer cells to chemotherapy agents.
Targeted Inhibition Of Multidrug Resistance-associated Protein 4 (MRP4) As A Therapeutic Strategy For Childhood Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$602,503.00
Summary
We have shown that a high tumour level of the gene, MRP4, confers a particularly poor outcome in children with the aggressive cancer neuroblastoma. Our results suggest that MRP4 can drive the growth of neuroblastoma cells, and that it does so by removing from the cancer cell a compound that normally regulates key cellular responses including survival and differentiation. We will explore this, and will also test promising inhibitors of MRP4 with therapeutic potential, that we have developed.
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.
Osteosarcoma is the most common tumour of bone. Recent success in targeting immune checkpoint blockers such as Programmed death-1 (PD-1) in genomically complex tumours suggests that osteosarcomas may be amenable to such strategies. We will characterise the role of the PD-1 pathway in osteosarcoma development and growth. Using preclinical mouse models we will investigate the biology of the PD-1 pathway and study its potential as a therapeutic target in advanced and resectable osteosarcoma.
Selective Targeting Of Apoptotic Pathways For Therapy
Funder
National Health and Medical Research Council
Funding Amount
$518,159.00
Summary
The cells of all animals possess the ability to commit suicide. When this natural process of cell death is dysfunctional, diseases such as cancer arise. New anti-cancer drugs aimed at targeting key components of the cell death machinery are showing promise in some patients, but not all. Our aim is to determine whether targeting other cell death components could be a more effective approach. We will also develop new chemicals that could one day allow such strategies to be applied in the clinic.
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.
ADAM Metalloprotease Inhibition For Treatment Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$770,925.00
Summary
Colorectal cancer (CRC) causes over 4000 deaths/year, typically from developing drug resistance and spreading to other organs (metastasis). These processes involve tumour cells called cancer stem cells (CSCs), which rely on specific cell surface proteins for survival and function. We are developing antibodies against one of these type of proteins, to test in mouse models of CRC. These already show promise in targeting CSCs and inhibiting drug-resistance and metastasis in mice.
Cyclin E1 As A Therapeutic Target In Women With High-grade Serous Cancer And Primary Treatment Failure
Funder
National Health and Medical Research Council
Funding Amount
$644,170.00
Summary
Ovarian cancer is the 5th most common cancer in women and the most lethal gynaecologic malignancy. We found tumours with extra copies of the CyclinE1 gene (CCNE1) are less likely to respond to standard treatment, and show reliance on its activity. Therefore, targeting CCNE1 may be a novel treatment strategy for these cancers. We will perform preclinical studies with therapeutic inhibitors towards the CCNE1 pathway and further explore the underlying biology of tumours with CCNE1 amplification.
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.
A Novel Approach To Restoration Of Tumour Suppression In Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$598,604.00
Summary
Loss of a tumour suppressor is a key event in every cancer, including lung cancer. Therefore restoration of the expression and/or activity of the tumour suppressor is an attractive approach to anti-cancer treatment. In order to restore tumour suppression, a detailed understanding of the mechanism by which a given tumour suppressor is regulated is required. This application focuses on our discovery of a novel mechanism by which a key tumour suppressor of lung cancer is regulated.