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.
Characterisation Of The Tumour Suppressor Function Of Caspase-2
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Aberrant cell death (apoptosis) is associated with many diseases including cancer. Apoptosis is mediated by a group of enzymes called caspases. Recently we have discovered that one of these enzymes, caspase-2, acts as a tumour suppressor. We now wish to validate this finding in several preclinical models of cancer and understand precisely how caspase-2 works to safeguard cells against cancer development. These studies will help better understand cancer and ways to treat it.
Molecular Characterisation Of Telomere Trimming And Its Role In Cell Proliferative Capacity
Funder
National Health and Medical Research Council
Funding Amount
$403,439.00
Summary
Telomeres are protective structures at the ends of chromosomes. Telomere length is a major determinant of how many times a cell can proliferate. We have recently discovered a rapid telomere shortening process that we have called telomere trimming. We will analyse the molecular details of this process to determine whether it could be used to shorten telomeres and stop cancer cell proliferation, and whether blocking it could increase cell proliferation in patients with short telomere syndromes.
Role Of Proline-rich Tyrosine Kinase 2 (Pyk2) In Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$85,254.00
Summary
Ovarian cancer is one of the most lethal gynaecological cancers in the developed world. Elevated levels of gonadotropin hormones and cell protein Pyk2 have been implicated in ovarian cancer. Our aim is to determine the role of Pyk2 in growth and metastasis of ovarian cancer when stimulated with gonadotropins. In addition, we aim to identify protein changes which occur in ovarian cancer when stimulated by gonadotropins in order to identify new biomarkers for the disease.
The Microenvironmental Niche In Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
It is well accepted that the cells in the local environment of cancers can help to promote the growth and spread of tumour cells. We have shown that a cell type known as the pericyte previously thought to be involved in controlling tumour expansion by affecting new blood vessel formation, may directly influence tumour growth, a notion that will be tested in human skin and ovarian cancer models. We will also test if pericyte markers can predict those cancer patients at greater risk of relapse.
Mechanisms Of Hedgehog Signaling In Small Cell Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$439,564.00
Summary
Some types of lung are very sensitive to chemotherapy, however they frequently relapse, at which time they become resistant to this form of treatment. This project investigates how embryonic signaling pathways, that normally function to regulate organ formation in development, are activated and promote tumor regrowth following chemotherapy for lung cancer.
Interaction Of TRF2 With DNA Repair Proteins In Alternative Lengthening Of Telomeres
Funder
National Health and Medical Research Council
Funding Amount
$297,246.00
Summary
10-15% of human cancers, including some of the most difficult-to-treat and aggressive, depend for their continuing growth on a molecular process called Alternative Lengthening of Telomeres (ALT). We have identified for the first time a protein whose normal role includes repressing ALT. We will study how this protein works, what its molecular partners are, and how these molecules interact with each other. This information is expected to lay the foundations for cancer treatments that target ALT.
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.
A Single Nucleotide Resolution Map Of A Cancer Associated Neochromosome
Funder
National Health and Medical Research Council
Funding Amount
$567,350.00
Summary
Neochromosomes (NCs) are large chromosomes which are not usually found in a normal cell. Well differentiated liposarcoma (WDLPS) is a tumour which is almost universally associated with the presence of NCs. We are using the approach of purifying the NC from a series of WDLPS cell lines, and using new techniques to derive the DNA sequence of the neochromosome. We will use this information to identify the genetic factors on the NC which are involved in the initiation or progression of WDLPS.
Determinants Of Response To Immune Checkpoint Inhibitors In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$1,021,487.00
Summary
Until recently, patients with melanoma were treated with single agent drugs that produced no improvement in overall survival. Today, almost 80% of patients will respond to new therapies and the 2-year survival is greater than 50%. Attention has turned to the combination of immunotherapies in order to improve patient responses. This research investigates the mechanisms of response and resistance to these therapies, in order to enhance the duration and rate of patient responses.