Targeting Adaptive Mechanisms To Endoplasmic Reticulum Stress In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
Melanoma is a major Australian health problem, but there is no curative treatment once the disease spreads beyond the skin. We will study the role the response of melanoma cells to stress conditions of an organelle called endoplasmic reticulum in determining sensitivity of melanoma to killing induced by therapeutic drugs. If successful, this study will provide much needed new insights into the resistance of melanoma to treatment and point to new treatment approaches against the disease.
NY-ESO-1 Expression As An Inducible Chemosensitivity Marker
Funder
National Health and Medical Research Council
Funding Amount
$113,237.00
Summary
Immunotherapy is a new concept treatment for lung cancer. Cancer testis antigen (CTA, eg NY-ESO-1) is an immunogenic molecule that was related with poor outcomes, but our recent studies have found that tumours that express NY-ESO-1 are more responsive to chemotherapy. We are also able to induce expression of NY-ESO-1 in cells that do not normally express it using demethylating agents. We aim to determine if we can increase the response to chemotherapy by using these drugs in combination.
The TOPGEAR Trial; Trial Of Preoperative Therapy For Gastric And Esophagogastric Junction Adenocarcinoma
Funder
National Health and Medical Research Council
Funding Amount
$1,974,558.00
Summary
While surgery to remove gastric (stomach) cancer has been traditionally accepted as the only way to potentially cure the disease, there have been several recent advances using chemotherapy and/or radiotherapy both before and after surgery. However doctors' opinions remain divided regarding the best treatments to give and in what order. This randomised clinical trial will address the important question of whether combined chemotherapy plus radiotherapy is more effective than chemotherapy alone in ....While surgery to remove gastric (stomach) cancer has been traditionally accepted as the only way to potentially cure the disease, there have been several recent advances using chemotherapy and/or radiotherapy both before and after surgery. However doctors' opinions remain divided regarding the best treatments to give and in what order. This randomised clinical trial will address the important question of whether combined chemotherapy plus radiotherapy is more effective than chemotherapy alone in improving cure rates for stomach cancer.Read moreRead less
Pathophysiology Of Oxaliplatin-induced Nerve Dysfunction And Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$281,255.00
Summary
When treating patients diagnosed with cancer, nerve dysfunction is a common complication of chemotherapy, particularly with oxaliplatin. Neurological symptoms develop in up to 90% of patients following oxaliplatin treatment. Neurotoxicity is a key factor in determining the dosage and frequency of current chemotherapeutic agants. Oxaliplatin therapy results in disabling neurological effects. Onset of neuropathy can be relatively fast or in other cases may develop months after therapy has been com ....When treating patients diagnosed with cancer, nerve dysfunction is a common complication of chemotherapy, particularly with oxaliplatin. Neurological symptoms develop in up to 90% of patients following oxaliplatin treatment. Neurotoxicity is a key factor in determining the dosage and frequency of current chemotherapeutic agants. Oxaliplatin therapy results in disabling neurological effects. Onset of neuropathy can be relatively fast or in other cases may develop months after therapy has been completed. The other chief problems encountered during chemotherapy can be overcome: nausea and vomiting can be treated; myelosuppression can be reversed. End organ toxicity such as neuropathy cannot be controlled. Despite the high incidence of neuropathy due to chemotherapy, the mechanisms involved remain poorly understood, particularly with newer therapies. The aim of the present study is to measure nerve function in oncology patients treated with oxaliplatin using a novel protocol, attempting ultimately to identify aspects of dysfunction that correlate with clinical abnormalities, so helping to pin-point the mechanisms responsible for neuropathy. Once identified, management strategies can be developed to better target the prevention and treatment of neuropathy in oncology patients treated with chemotherapy.Read moreRead less
Molecular Determinants Of Risk, Progression And Treatment Response In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$15,161,573.00
Summary
The investigators, all associated with the Melanoma Institute Australia, have recruited numerous people and biospecimens in order to study the causes, subtypes and treatment strategies in melanoma. The team aims to develop a scientific basis for improved 1) management of individuals at high risk of melanoma development and progression, and 2) treatment of patients with early and disseminated melanoma, thereby contributing to improved prospects of successfully treating this dangerous cancer.
Assessing And Optimising Anti-Cancer Drug Utilisation
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Cancer is increasingly common in Australia and often treated with expensive drugs tested in idealised settings within clinical trials. It is vital to collect real world data about how cancer treatments are used in Australia. This research will use routinely collected health care data to determine how anti-cancer drugs are used in the real world, how effective they are in treating cancer, and identify areas for improvement to promote effe ctive, appropriate and equitable use of anti-cancer drugs.
Post-operative Concurrent Chemo-radiotherapy Versus Post-operative Radiotherapy In High Risk Cutaneous Squamous Cell Carcinoma Of The Head And Neck
Funder
National Health and Medical Research Council
Funding Amount
$252,000.00
Summary
Squamous cell carcinoma of the skin is one of the most common cancers affecting Australians. The majority are readily cured with simple local therapy, such as surgery. However some patients develop advanced disease requiring surgery and post-operative radiotherapy. Despite this, some patients do not achieve cure. This study aims to improve cure rates for these patients by comparing post-operative radiotherapy (control arm) to post-operative chemo-radiotherapy(experimental arm).
Prof. Simes will lead and develop research at the NHMRC Clinical Trials Centre in collaboration with major national and international cooperative groups. Research themes include integrating molecular science with trial design and embedding research routinely in health care. Projects include surgery for rectal cancer; novel targeted therapy in gastric cancer; aspirin to prevent colon cancer; placental transfusion for preterm babies; risk in heart disease; economic assessment of clinical trials.
OVERCOMING RESISTANCE OF HUMAN MELANOMA TO CHEMOTHERAPY
Funder
National Health and Medical Research Council
Funding Amount
$499,500.00
Summary
Melanoma is the third most common cancer in women and men respectively. In NSW alone approximately 400 die each year from the disease. The main treatment of melanoma is surgical removal of the primary tumor on the skin but once the disease spreads beyond the skin to other organs there is no curative treatment. This study will identify whether resistance of melanoma to chemotherapy is due to failure to induce sufficient levles of pro-apoptotic BH3 only proteins and-or activation of apoptosis resi ....Melanoma is the third most common cancer in women and men respectively. In NSW alone approximately 400 die each year from the disease. The main treatment of melanoma is surgical removal of the primary tumor on the skin but once the disease spreads beyond the skin to other organs there is no curative treatment. This study will identify whether resistance of melanoma to chemotherapy is due to failure to induce sufficient levles of pro-apoptotic BH3 only proteins and-or activation of apoptosis resistance pathways. The results will be directly relevant to subsequent clinical trials in melanoma paients. Apoptosis may be triggered by chemotherapeutic agents but human melanoma shows wide variability in apoptotic responses to chemotherapy. Recent studies have shown that the Bcl-2 family of pro- and anti-apoptotic proteins and inhibitor of apoptosis proteins appear to be key regulators of the (mitochondrial) apoptosis pathway induced by chemotherapy. The activity of the proteins appear to be regulated by several signal pathways in the cell which may be activated by signals external or intrinsic to the cell. We wish to characterize the proteins involved in chemotherapy induced apoptosis, assess their variability between melanoma cells that are sensitive or resistant to apoptosis and characterize the signal pathways involved in regulating the proteins in human melanoma.Read moreRead less
The Role Of Microtubule Composition In The Efficacy Of Antimicrotubule Agents In Paediatric Malignancy
Funder
National Health and Medical Research Council
Funding Amount
$173,380.00
Summary
To enhance the management of both childhood and adult cancers improved understanding of the processes responsible for tumour aggressiveness and drug resistance are required. Microtubules are important structural components of cells which are crucial for normal cell division. This makes microtubules excellent targets for anticancer drugs which can disrupt microtubules and kill cancer cells. This proposal will identify whether the microtubule composition of a tumour cell will predict for the aggre ....To enhance the management of both childhood and adult cancers improved understanding of the processes responsible for tumour aggressiveness and drug resistance are required. Microtubules are important structural components of cells which are crucial for normal cell division. This makes microtubules excellent targets for anticancer drugs which can disrupt microtubules and kill cancer cells. This proposal will identify whether the microtubule composition of a tumour cell will predict for the aggressiveness of certain cancers, and whether this influences which tumours will respond to the vinca alkaloids. The vinca alkaloids are an important class of natural product drugs which disrupt microtubules and are particularly effective in the treatment of adult and childhood cancers. Unfortunately, some cancer cells fail to respond to this treatment due to the development of drug resistance. This proposal addresses vinca alkaloid resistance in children?s cancer and will determine why certain cancer cells fail treatment. Furthermore, this study will identify the role of certain components of microtubules that appear to be related to drug resistance in leukaemia and neuroblastoma cells and whose role is unknown. Chemotherapeutic drugs, such as the vinca alkaloids, are important in the treatment of cancer and knowledge about their interaction with their cellular target will improve the design of new drugs and treatment outcome.Read moreRead less