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A Lineage Specific Pathway For Progression Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$485,746.00
Summary
Melanoma is an insidious cancer, and its incidence has increased dramatically over the past four decades. Melanoma has an almost universally poor prognosis once metastasis has occurred. There are currently no treatment regimens that have a significant impact on prolonging survival or decreasing mortality from metastatic melanoma. Our preliminary data has shown the importance of a factor found in normal melanocytes in control over expression of a separate factor required for invasion and metastas ....Melanoma is an insidious cancer, and its incidence has increased dramatically over the past four decades. Melanoma has an almost universally poor prognosis once metastasis has occurred. There are currently no treatment regimens that have a significant impact on prolonging survival or decreasing mortality from metastatic melanoma. Our preliminary data has shown the importance of a factor found in normal melanocytes in control over expression of a separate factor required for invasion and metastasis of melanoma. These markers could serve as an important diagnostic marker for melanoma. Further, they may be suitable drug targets for the prevention and treatment of metastatic melanoma, and will advance our understanding of how melanoma spreads.Read moreRead less
MECHANISMS OF MOTILITY AND METASTASIS In BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$209,505.00
Summary
The broad aim of this proposal is to elucidate novel molecular mechanisms of breast cancer cell motility that are relevant to metastasis or the spread of cancer. The function of two genes will be studied. We propose that (1) reduced on-random motile (ROM) regulates the speed of cancer cell movement, and (2) Neural Wiskott-Aldrich syndrome protein (N-WASP) regulates the directional component of cell movement. We will relate the function of ROM and N-WASP to rapid, linear walking along collagen fi ....The broad aim of this proposal is to elucidate novel molecular mechanisms of breast cancer cell motility that are relevant to metastasis or the spread of cancer. The function of two genes will be studied. We propose that (1) reduced on-random motile (ROM) regulates the speed of cancer cell movement, and (2) Neural Wiskott-Aldrich syndrome protein (N-WASP) regulates the directional component of cell movement. We will relate the function of ROM and N-WASP to rapid, linear walking along collagen fibres in live tumours and to breast cancer metastasis to the lung. ROM will be inhibited in breast cancer cells and we expect increases in both the speed of cell movement and metastasis. Therefore, ROM functions as a suppressor of metastasis. Inhibition of N-WASP, however, is expected to compromise both the directionality of cell movement and metastasis. N-WASP is therefore, a promoter of metastasis. At the completion of this work, the regulatory mechanisms of motility and metastasis by ROM and N-WASP will be defined. This will facilitate the development of biologically targeted agents for ROM and N-WASP that can be used to control metastasis. In addition, these agents that target the motility pathway are appropriate for use in combined therapy with agents that target a different pathway such as survival or growth. This will significantly improve disease control rates or the proportion of patients with partial or complete disease regression. This proposal addresses the National Health Priority, cancer, and related National Research Priority, ageing well and ageing productively, where in the longer term, we will be able to create new and much needed therapy for metastasis.Read moreRead less
REGULATION OF MICROTUBULE DYNAMICS BY LIM KINASE1 (LIMK1)
Funder
National Health and Medical Research Council
Funding Amount
$386,020.00
Summary
Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. We have found that LIMK1 is very important in controlling the polymerisation of one of the most ....Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. We have found that LIMK1 is very important in controlling the polymerisation of one of the most abundant molecules in the cell, actin. We have now preliminary data to show that LIMK1 also controls another important cellular protein, tubulin. Changes in tubulin polymerisation are of extreme importance for cell division and drugs affecting the state of tubulin are very potent as anti-cancer drugs. The goals of this research are: (1) To confirm that LIMK1 regulates the polymerisation of tubulin and (2) To demonstrate that LIMK1 regulates tubulin polymerisation by controlling the activity of p25, a protein involved in tubulin polymerisation that is modified by LIMK1. The results from this research will be highly significant because LIMK1 is a novel drug development target. Drugs that inhibit this protein may block the ability of tumours to invade and metastasise. Therefore, we have to identify the other functions of LIMK1 to eliminate the possibility that drugs that inhibit LIMK1 and metastasis don't affect other organs and cells in the body. New molecules regulated by LIMK1 may also be suitable targets for drug development because through their inhibition we may also regulate other LIMK1 activities and possibly metastasis.Read moreRead less