Role Of LncRNA IDH1-AS1 In Regulating C-Myc Driven-glycolysis And Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$685,043.00
Summary
It is thought that understanding cancer metabolism will reveal vulnerabilities that can be exploited in the clinic. Indeed, compared to most normal cells, cancer cells utilise different fuels to sustain proliferation and to adapt to their environment. Herein we have discovered a molecular switch that regulates the key metabolic enzyme IDH1 and show this controls tumour growth. Given this switch may be active in 50% of cancers we anticipate our work will have significance to many cancer types.
Interplay Between Metabolic Reprogramming And Oncogenic Signalling In The Cellular Response To Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$654,035.00
Summary
Chemotherapy resistance is a major barrier to the treatment of triple-negative breast cancer (TNBC). We seek to uncover an intimate link between cell metabolism and oncogenic signalling pathways in regulating the cellular response to chemotherapy. Our studies will identify a critical mechanism limiting the therapeutic efficacy of chemotherapy and investigate combination therapy strategies that could improve the treatment of TNBC.
Investigating Signalling Pathways That Mediate Suppression Of Anoikis By Chemokine Receptors In Metastatic Breast Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$597,349.00
Summary
This research aims at understanding the "nuts and bolts" of the main killer in cancer patients - tumour metastasis. We will look for molecules that are specific to metastatic tumour cells that transmit signals from the cell surface to the cell "suicide" machinery and prevent metastatic cancer cell death.
Mechanisms Of Mcl-1- And Bcl-2-mediated Resistance To Apoptosis
Funder
National Health and Medical Research Council
Funding Amount
$439,796.00
Summary
Anti-cancer therapies that target either the mitochondrial or death receptor pathways of apoptotic cell death are being developed and in clinical trials. In certain cancer cells, the tBid protein links the two pathways, making the death receptor pathway dependent on the mitochondrial pathway. Our studies will test how tBid links the two pathways and how the link might be bypassed, potentially indicating means of improving the effectiveness of treating cancer by targeting death receptors (e.g. TR ....Anti-cancer therapies that target either the mitochondrial or death receptor pathways of apoptotic cell death are being developed and in clinical trials. In certain cancer cells, the tBid protein links the two pathways, making the death receptor pathway dependent on the mitochondrial pathway. Our studies will test how tBid links the two pathways and how the link might be bypassed, potentially indicating means of improving the effectiveness of treating cancer by targeting death receptors (e.g. TRAIL).Read moreRead less
Controlling The Pro-survival Protein Mcl-1: Discovering Novel Opportunities And Developing Innovative Approaches To Target Mcl-1 For Treating Cancers
Funder
National Health and Medical Research Council
Funding Amount
$749,415.00
Summary
Cancer cells are often sustained by evading cell death. Thus, a promising approach to develop new cancer treatments aims to restore their ability to commit cell suicide. Proteins related to Bcl-2 are, in this regard, attractive targets because they are prominent barriers to cell death. This project seeks to uncover how a Bcl-2 relative, Mcl-1, is regulated, and to explore how the mechanisms that underpin these processes can be targeted in cancers (melanomas, leukemias) that it sustains.
Fzd receptors are often upregulated in gastric cancer, and recent studies have shown that targeting these receptors has be effective at reducing cancer cell growth in other cancers including prostate and breast. This project will use cutting edge technology to firstly determine the specific requirement for Fzd receptors during gastric cancer and then determine the therapeutic benefit of using an antibody to target these receptors in mouse models and human gastric cancer cells.
Developing Cancer Therapies That Target Chromosomal Instability
Funder
National Health and Medical Research Council
Funding Amount
$644,126.00
Summary
A significant reason why late-stage cancers are hard to treat with drugs is because the tumour cells show genetic variability, always producing new variants that sooner or later get around the drugs. We intend to combat this by targeting the ability of cancer cells to vary genetically - we are discovering ways to specifically kill genetically unstable cells. This prevents the cancer from developing drug resistance as well as having less side effects on the patient's normal cells.
The Ghrelin Axis As A Target For Prostate Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$585,497.00
Summary
Prostate cancer affects one in nine Australian men in their lifetime, and although there have been great advances in treatments, advanced prostate cancer remains incurable. Current treatments often lead to side effects which affect quality of life. We have found that the appetite hormone, ghrelin, stimulates prostate cancer cell growth and may be a useful target for prostate cancer therapy. We predict that targeting the ghrelin axis will prevent some of the side effects of other treatments that ....Prostate cancer affects one in nine Australian men in their lifetime, and although there have been great advances in treatments, advanced prostate cancer remains incurable. Current treatments often lead to side effects which affect quality of life. We have found that the appetite hormone, ghrelin, stimulates prostate cancer cell growth and may be a useful target for prostate cancer therapy. We predict that targeting the ghrelin axis will prevent some of the side effects of other treatments that reduce quality of life for patients.Read moreRead less
ALT-associated PML Bodies: Keys To The Biology And Treatment Of An Important Subset Of Cancers
Funder
National Health and Medical Research Council
Funding Amount
$813,614.00
Summary
Alternative Lengthening of Telomeres (ALT) is a molecular mechanism used by ~10% of cancers to sustain their relentless growth. ALT is common in sarcomas and brain tumours which are difficult to treat. ALT cancers contain nuclear structures called ALT-associated PML nuclear bodies (APBs) which may be part of the ALT machinery. This research will investigate characteristics of APBs and how they are formed, and will use this information to identify drugs to treat ALT tumours.
Real-time Optical Window Imaging Of AKT-FRET Biosensor Mice To Maximise PI3K/AKT Drug Targeting Within The Hypoxic Microenvironment Of Pancreatic Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$683,447.00
Summary
Inefficient drug response in solid tumour tissue is often a limiting factor in the clinical effectiveness of cancer therapies. Using cutting-edge imaging technology and 3D models that mimic the disease, we have mapped areas of poor drug response within distinct regions of tumours with low oxygen levels known as hypoxia. Here, we will specifically target factors limiting efficient drug targeting in these areas to improve the encouraging anti-cancer profile of AKT inhibitors in pancreatic cancer.