Biological And Clinical Characterisation Of Human Phosphatidylinositide 3-kinase Mutations
Funder
National Health and Medical Research Council
Funding Amount
$33,626.00
Summary
The frequency of PI3K mutations in tumours, suggests that PI3K is one of the most common human oncogenes. Understanding the biological and biochemical significance of these mutations will provide new insights into the biology of human tumourigenesis and further our understanding of the consequence pathways and the progression of human tumours. Such knowledge will help us to identify more effective markers of prognosis, diagnosis, early detection of cancer and design new anti-cancer therapy.
Phosphatidylinositol 3-kinase Mutations Associated With Ovarian, Colon And Breast Tumours
Funder
National Health and Medical Research Council
Funding Amount
$154,000.00
Summary
Colorectal and breast cancers are the two most common registrable cancers in Australia and are second only to lung cancer in the total number of cancer deaths each year (4,678 and 2,612 deaths in 1997 for colorectal and breast, respectively). Ovarian cancer kills a further 740 women each year (Source: Cancer in Australia 1997, AIHW and AACR 2000). Thus, on average, one Australian dies of colorectal, breast or ovarian cancer every hour! Clearly, these are major diseases with a significant impact ....Colorectal and breast cancers are the two most common registrable cancers in Australia and are second only to lung cancer in the total number of cancer deaths each year (4,678 and 2,612 deaths in 1997 for colorectal and breast, respectively). Ovarian cancer kills a further 740 women each year (Source: Cancer in Australia 1997, AIHW and AACR 2000). Thus, on average, one Australian dies of colorectal, breast or ovarian cancer every hour! Clearly, these are major diseases with a significant impact on our society. Unfortunately, though, we still do not understand the basic molecular and-or biochemical abnormalities that initiate and-or drive the development of these cancers. Recent functional and genetic studies in a number of different tumour types (including colon and ovarian) have suggested that members of the phosphatidylinositol 3-kinase (PI3K) enzyme family may be oncogenes (cancer-causing genes). However, strong evidence confirming a causal role for PI3K in human cancer is yet to be reported. Our research proposal outlines a study to address this issue. We have preliminary data demonstrating mutations in at least one member of this enzyme family in a number of tumours. We now propose to undertake a comprehensive analysis of the spectrum, and frequency, of PI3K mutations that occur in colon, breast and ovarian tumours. These studies will allow us to make a definitive assessment of the role of PI3K in the development human cancer. In addition to furthering our understanding of the processes involved in the initiation and progression of human tumours, this project also has the potential to identify new markers for the early detection of cancer and novel targets for new anti-cancer therapies.Read moreRead less
Biological And Clinical Characterisation Of Human Phosphatidylinositide 3-kinase Mutations
Funder
National Health and Medical Research Council
Funding Amount
$553,776.00
Summary
Colorectal and breast cancers are the two most common registrable cancers in Australia and are second only to lung cancer in the total number of cancer deaths each year (4,678 and 2,612 deaths in 1997 for colorectal and breast, respectively). Ovarian cancer kills a further 740 women each year (Source: Cancer in Australia 1997, AIHW and AACR 2000). Thus, on average, one Australian dies of colorectal, breast or ovarian cancer every hour! Clearly, these are major diseases with a significant impact ....Colorectal and breast cancers are the two most common registrable cancers in Australia and are second only to lung cancer in the total number of cancer deaths each year (4,678 and 2,612 deaths in 1997 for colorectal and breast, respectively). Ovarian cancer kills a further 740 women each year (Source: Cancer in Australia 1997, AIHW and AACR 2000). Thus, on average, one Australian dies of colorectal, breast or ovarian cancer every hour! Clearly, these are major diseases with a significant impact on our society. Unfortunately, though, we still do not understand the basic molecular and-or biochemical abnormalities that initiate and-or drive the development of these cancers. Our laboratory has recently reported a high frequency of mutation of the phosphoinositide 3-kinase (PI3K) gene PIK3CA in breast, colorectal and ovarian tumours. This work, funded by the NHMRC, has not only confirmed that PI3K is a bone fide human oncogene but also that mutations in the PI3K family of genes are one of the most common, and thus potentially one of the most important, genetic abnormalities in solid human tumours. In the current proposal, we aim to extend and complement our genetic studies by addressing the biological consequences and clinical significance of the mutations we have identified. This will provide crucial new insights into the biology of human tumourigenesis and further our understanding of the critical pathways and processes involved in the initiation and progression of human tumours. Such knowledge will help us to identify novel markers for diagnosis, prognosis and the early detection of cancer and enable a rational approach to the design of new anti-cancer therapies.Read moreRead less
Understanding The Role Of PI 3-kinase Mutations In Gastrointestinal Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$283,880.00
Summary
Mutations in the PIK3CA gene are frequently found in bowel cancers but it remains unclear exactly how these mutations are involved in cancer development. We will exploit a unique mouse model to explore the role of PIK3CA mutations in the initiation, progression and-or metastasis of gastrointestinal cancers. This work will provide critical new insights into the biology of PIK3CA mutations and lead to the development of better models for the testing of new anti-cancer therapies.
Studies On The Tumour-associated PIK3CA(H1047R) Mutation Using In Vitro And In Vivo Models Of Breast And Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$583,312.00
Summary
PIK3CA mutations are frequently found in breast and ovarian cancers but how they cause cancer is not clear. We will exploit a unique mouse model to investigate the functional effects of PIK3CA mutations in cells and their role in cancer development. Understanding the mechanisms by which PIK3CA mutations regulate cell function and drive tumour growth will allow the rationale design of novel anti-cancer agents that specifically target this important cancer pathway.
Studies On The Role Of The P101 Component Of The Class 1B PI 3-Kinase In Cell Migration And Activation.
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
This research will determine the biological role of a protein of unknown function that is likely to participate in movement of white blood cells through the body. The outcome of this research will increase our basic knowledge of how the immune system functions and could lead to alternate therapeutic strategies for the control of autoimmune diseases.
Targeting A Novel Anti-platelet Mechanism For Improved Anti-thrombotic Therapy
Funder
National Health and Medical Research Council
Funding Amount
$985,938.00
Summary
Blood clots cause heart attacks and most strokes, which are the most common cause of death in the world. Platelets are the cells in the blood that form these clots, and drugs that prevent platelet function are the major approach for heart attack and stroke prevention. However, many patients are resistant to the effects of existing therapies. These studies will develop a unique approach to prevent platelet function that may help overcome the limitations of current drugs.