Differentiation Therapy Of Acute Myeloid Leukaemia: Combining RAR-agonists And G-CSF.
Funder
National Health and Medical Research Council
Funding Amount
$449,500.00
Summary
The application of cancer treatments that target specific molecules hold significant promise. However to apply these treatments detailed knowledge is required of the how the molecular targets function in cells. Our previous work using normal blood cells has identified two genes ( MAD1 and p27KIP1 ) that are required for the effects of one such targeted treatment that is aimed at the retinoic acid receptor alpha. We propose to test this treatment in mouse models of human leukaemia and in human le ....The application of cancer treatments that target specific molecules hold significant promise. However to apply these treatments detailed knowledge is required of the how the molecular targets function in cells. Our previous work using normal blood cells has identified two genes ( MAD1 and p27KIP1 ) that are required for the effects of one such targeted treatment that is aimed at the retinoic acid receptor alpha. We propose to test this treatment in mouse models of human leukaemia and in human leukemia cells grown in the laboratory. By deleting the genes for MAD1 and p27KIP1 we will determine if leukaemias lacking these genes fail to respond to treatments targeting the retinoic acid receptor alpha. We will also test if treatments that target retinoic acid receptors in combination with G-CSF, a protein that has previously been demonstrated to have anti-leukaemic activity, can work together to block growth of leukaemic and genetically modified cells. Together these studies will help define classes of leukamias that either will or will not respond to treatments aimed at retinoic acid receptor to better target future leukemia treatments.Read moreRead less
LIM KINASE 1 (LIMK1) AND METASTASIS, THE SEARCH FOR LIMK1 INHIBITORS
Funder
National Health and Medical Research Council
Funding Amount
$461,250.00
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. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic ....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. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic tumours in mice, and (2) introduction of this protein into tumour cells makes them more invasive. In addition, we find that the level of LIMK1 is much higher in human tumour cell lines that have the propensity to easily form tumours in mice. Also, measuring the level of this protein in cancer cells that spread to other organs shows that it is at significantly elevated levels when compared to normal tissue. The goals of this research are to: (1) understand whether the ability of LIMK1 to regulate tumour spreading and invasiveness correlates with its ability to control metastasis; (2) examine in human tumour samples whether the levels of LIMK1 correlate with the development of metastatic tumours; and (3) search for drugs that can inhibit the activity of this protein. The results from this research will be highly significant because LIMK1 levels are likely to be an important marker for which tumours will become metastatic. It is possible that, at the time of tumour diagnosis, LIMK1 measurements will enable the clinician to predict whether an individual tumour will become metastatic. Secondly, this protein is a novel drug development target. Drugs that inhibit this protein may block the ability of tumours to invade and metastasise.Read moreRead less