Targeting Microtubules To Overcome Chemoresistance In Pancreatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$594,336.00
Summary
Pancreatic cancer is a devastating disease with a dismal prognosis because it is extremely resistant to chemotherapy agents. We plan to examine the expression of proteins called microtubules in pancreatic cancer and assess their role in drug resistance. It is anticipated that the findings of these studies will lead to the development of effective approaches to sensitise the cancer cells to chemotherapy agents.
Microtubule Cytoskeleton In Tumourigenesis And Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$612,885.00
Summary
Over one million cases of lung cancer are diagnosed each year worldwide, making this the leading cause of cancer death. Advanced non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases. We have identified a protein called ?III-tubulin that is often highly expressed in aggressive and drug resistant NSCLC, and is involved in tumour formation. We will examine how ?III-tubulin is working and identify ways to target this protein to stop tumour growth.
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
Molecular And Cellular Determinants Of Tubulin-targeted Drug Action
Funder
National Health and Medical Research Council
Funding Amount
$484,500.00
Summary
Cancer is the leading cause of death in developed countries. Despite advances in the use of combination chemotherapy, drug resistance is the major cause of treatment failure. An important component in the treatment of many childhood and adult cancers are the antimicrotubule agents. These drugs target an important part of the cell skeleton called the tubulin-microtubule system that is responsible for many important events including cell division. It is the ability of these drugs to disrupt cell d ....Cancer is the leading cause of death in developed countries. Despite advances in the use of combination chemotherapy, drug resistance is the major cause of treatment failure. An important component in the treatment of many childhood and adult cancers are the antimicrotubule agents. These drugs target an important part of the cell skeleton called the tubulin-microtubule system that is responsible for many important events including cell division. It is the ability of these drugs to disrupt cell division in cancer cells that makes them so effective and such important targets for new drug design. Unfortunately, the reasons why tumours develop resistance to these drugs or even why some tumours do respond well is not understood. This proposal will determine how the makeup and stability of the tubulin-microtubule proteins influences how these drugs work in both childhood and adult tumour cells. Finally, components of drug resistant tumour cells will be examined using technology that allows us to simultaneously separate and identify hundreds of proteins some of which may provide useful targets for the design of new drugs for the treatment of cancer. To improve cancer survival rates it is essential to accurately target the use of existing drugs and to identify new targets for anticancer drug development.Read moreRead less