DOES BCL-G, A BH3-ONLY PROTEIN, PLAY A ROLE IN INFLAMMATION-ASSOCIATED COLON CANCER?
Funder
National Health and Medical Research Council
Funding Amount
$418,587.00
Summary
Deregulation of the function of several members of the Bcl-2 family has been shown to be an aggravating factor in autoimmune diseases and cancer. Bcl-G is a new and poorly characterized member of this family. We have produced essential tools to study the physiological function of Bcl-G, and discovered that it plays a role in inflammatory bowel disease. We now plan to investigate its possible role in inflammation-associated colon cancer.?
Investigation Of DUSP5 As A Novel Tumour Suppressor Gene In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$578,268.00
Summary
Colon cancer is the second leading cause of cancer related death in Australia. Understanding the genetic causes of this disease are essential to developing new treatment strategies. The goal of this study is to understand the role of the DUSP5 gene in colon cancer. The findings of this study has the potential to further our understanding of how colon cancers arise and for identifying patients likely to respond to specific existing treatments.
Role Of The EHF Transcription Factor In Regulating The Differentiation Status Of Colon Cancers
Funder
National Health and Medical Research Council
Funding Amount
$621,950.00
Summary
New treatment strategies for colon cancer are urgently needed. This application will test a novel approach for treating colon cancer based on the re-induction of differentiation of colon cancer cells, by reactivating a gene called EHF. We expect this to reduce the propensity for colon cancer cells to spread to distant organs and to increase their sensitivity to chemotherpay. This has the potential to significantly benefit the clinical management of patients with this disease.
This project aims to develop a new therapy for colorectal cancer (CRC). We have already demonstrated that a molecule called PAK1 is the master regulator of several intracellular signalling pathways, and is essential for CRC growth and invasion. We now plan to study whether inhibitors that block PAK1 activity can prevent the growth of human CRC cells in the laboratory or their development into tumours in animals.
Mechanical Factors In Normal Human Colonic Motility
Funder
National Health and Medical Research Council
Funding Amount
$650,023.00
Summary
Abnormal human colonic contractions cause significant medical, societal and financial burdens. Diagnosis and treatment of motility disorders requires an understanding of normal colonic contractility against which to measure dysfunction. Through state-of-the-art recording and analytical techniques, developed by the applicants, this project will provide the first clear description of normal human colonic motor patterns and how they are generated.
Therapeutic Targeting Of The Colorectal Cancer Epigenome
Funder
National Health and Medical Research Council
Funding Amount
$537,045.00
Summary
Enhancer RNAs (eRNAs) are a new class of noncoding RNA molecules that have been linked to diverse functions that impinge on cancer, but their clinical relevance is unknown. Our work shows that distinct eRNAs are expressed in a subset of cancer and predict which cancer will respond to a cancer therapeutic agent called a BET inhibitor. Our proposal uses sophisticated preclinical models and cutting edge technology to investigate the functional role of enhancers and enhancer templated RNA in cancer.
Investigating The Roles Of The Wnt And Notch Signalling Systems In Colon Cancer Crypt Biology
Funder
National Health and Medical Research Council
Funding Amount
$604,439.00
Summary
Colon cancer occurs because of mutations to a tumour suppressor gene. These mutations alter the growth and positional signals for the cancer cells. This project aims to produce a computer model of the regulatory processes in normal colonic cells, to discover why the mutations lead to cancer and to discover rational drug targets for interfering with the growth of colon cancer cells.
Personalised Medicine Markers Of Anti-EGFR Antibody Therapy In Metastatic Colorectal Cancer: Accelerating Clinical Translation With Collaborative Meta-analyses Based On Individual-participant Data
Funder
National Health and Medical Research Council
Funding Amount
$300,953.00
Summary
When selecting cancer therapy we take into account ‘biomarkers’, biological cancer characteristics that predict treatment success. We will work with an international group, the Advanced Colorectal Cancer Database, to analyse individual patient clinical trial data. We intend to validate biomarkers used to select treatment with cetuximab or panitumumab. Cancer genes called KRAS, NRAS, PTEN, PIK3CA, EREG and BRAF will be examined. Our study will provide best evidence for personalised treatment.
Colorectal cancer is the third leading cause of cancer related death in Australia. While there are now a number of treatment options for patients with colon cancer, there is significant variability in response among patients to individual drugs. This NHMRC project grant will seek to identify genetic markers which predict the likelihood of a patient responding to a specific therapy. This will enable individual patients to be treated with the drug most likely to be of benefit to them.
Chemotherapy causes a massive depletion of blood-producing cells in the bone marrow. This results in a condition known as myelosuppression that has many harmful side effects for cancer patients. Our aim is to develop a safe and inexpensive approach that will specifically protect the blood-producing cells from chemotherapy but leave the cancer cells sensitive. If this treatment shows significant benefits in mouse models of cancer then the establishment of clinical trials will be initiated.