New Drugs To Counteract The Side Effects And Premature Ageing Caused By Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$577,658.00
Summary
During cancer treatment, commonly used chemotherapy drugs cause profound side effects that include pain, nausea, heart problems, hair loss and can affect almost every system in the body. Even after chemotherapy treatment has stopped, cancer survivors face an increased risk of diseases which resemble the effects of old age. We are testing newly discovered anti-ageing molecules for their ability to reduce these side effects, and drastically improve the quality of life for cancer patients.
AKR1C3 As A Potential Biomarker For Sensitivity Of T-lineage Acute Lymphoblastic Leukaemia To The Pre-prodrug PR-104
Funder
National Health and Medical Research Council
Funding Amount
$327,797.00
Summary
Multiagent chemotherapy is the most effective modality for the treatment of childhood ALL, the most common paediatric malignancy. Despite dramatic improvements in survival over the past 40 years, relapsed ALL remains one of the most common causes of death from disease in children. Therefore, innovative strategies are needed to benefit those children who respond poorly to established therapy. This application will test a novel therapy for a very aggressive subtype of childhood leukaemia.
NEU-HORIZONS: The Neuroprotection And Therapeutic Use Of Riluzole For The Prevention Of Oxaliplatin Neurotoxicity Study.
Funder
National Health and Medical Research Council
Funding Amount
$382,402.00
Summary
Colorectal cancer is the second most commonly diagnosed cancer in Australia, with more than 13500 cases recorded annually. Oxaliplatin is an effective chemotherapy for the treatment of colorectal cancer. The major side-effect of oxaliplatin is the development of nerve damage that leads to loss of feeling in the hands and feet and significant disability. The aim of this study is to conduct a trial of a new treatment for oxaliplatin-induced nerve damage.
Multidrug Resistance Protein 1 Inhibitors To Sensitise Cancers To Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$840,166.00
Summary
Multidrug resistance protein 1 (MRP1) is often present at high levels in cancer cells, where it pumps chemotherapy drugs back out, causing drug resistance. Inhibitors that block MRP1 would increase the effectiveness of chemotherapy. We have developed MRP1 inhibitors with promising activity in cancer cells and mouse tumours and will now develop these inhibitors for clinical application and commercialisation.
Improving Outcomes For Patients Receiving Outpatient Chemotherapy Through A Shared Care Pathway Intervention
Funder
National Health and Medical Research Council
Funding Amount
$623,887.00
Summary
Many cancer patients receiving chemotherapy treatment continue to experience serious side effects at home, where they struggle to self-manage and often go to hospital after symptoms have worsened. We have developed an innovative clinical pathway involving the provision of home-based assessment, clinical care and advice by community nurses, which aims to help patients without creating new health service positions. Our study will test if the pathway decreases unplanned hospital visits, improves pa ....Many cancer patients receiving chemotherapy treatment continue to experience serious side effects at home, where they struggle to self-manage and often go to hospital after symptoms have worsened. We have developed an innovative clinical pathway involving the provision of home-based assessment, clinical care and advice by community nurses, which aims to help patients without creating new health service positions. Our study will test if the pathway decreases unplanned hospital visits, improves patient well-being and is cost-effective.Read moreRead less
Examination Of The Molecular Pharmacology Of Anthracyclines Induced Via Their Interaction With Iron
Funder
National Health and Medical Research Council
Funding Amount
$618,401.00
Summary
Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and ....Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and haem synthesis. Hence, this effect probably contributes to the cytotoxic activity of anthracyclines on the heart. We showed that novel drugs developed in my lab that bind Fe called chelators show high activity in animals (DR4) and prevent anthracycline-mediated Fe accumulation in ferritin. Importantly, Fe chelators have been shown to inhibit anthracycline-mediated cardiotoxicity. Indeed, the clinically used cardioprotective agent, ICRF-187, is actually an Fe chelator (5, DR6). However, ICRF-187 is not totally successful in terms of its cardioprotective effects and can cause myelosuppression (5, DR6). While the clinically used chelator, desferrioxamine (DFO), can prevent anthracycline-mediated cardiotoxicity, its poor membrane permeability limits its effectiveness. Our chelators are highly permeable and overcome the disadvantages of DFO (DR4). Thus, they are vital to examine for preventing anthracycline-mediated cardiotoxicity. In this proposal we will examine the changes in Fe metabolism induced by anthracyclines and test the hypothesis that novel Fe chelators may prevent the cardiotoxicity of these agents. We also aim to be the first to assess if preparation of anthracyclines which cannot bind iron prevents their cardiotoxicity. This will be done by preparing metal complexes of these drugs which prevent Fe-binding eg. anthracycline-zinc complexes. These studies are important for the development of less cardiotoxic forms of these very useful anti-tumour agents.Read moreRead less
The Trans Tasman Radiation Oncology Group is an experienced research group conducting cancer clinical trials involving radiotherapy (RT) in order to improve cure rates, quality of life and to reduce side-effects of treatment. Fifty per cent of all cancer patients need RT as part of their treatment. The aim of the proposal is to strengthen the quality and safety of RT trials by (a) enabling rapid review and checking of treatment by electronic means and (b) improve trial design.
Long-term Nerve Damage In Cancer Survivors: Identification Of Risk Factors And Optimal Assessment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$850,172.00
Summary
Nerve damage following chemotherapy treatment leads to early treatment cessation and long-lasting disability, developing with commonly used chemotherapies. There is a critical need to understand the mechanisms, optimize clinical assessment and develop interventions to prevent nerve damage. This project is designed to detect the impact of long-term nerve damage in cancer survivors and develop a risk profile based on clinical, neurophysiological and genetic factors.
Benefit Of 2D-strain Surveillance In Improving Cardiovascular Outcomes In Cancer Patients Undergoing Cardiotoxic Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$2,391,979.00
Summary
Cancer survivors are susceptible to heart failure (HF) caused by heart muscle damage from chemotherapy. The current testing for this problem is based on a measure that cannot identify minor changes of cardiac function. Cardiac strain is a sensitive new marker of cardiac function which is predictive of overt dysfunction & HF. This study seeks to identify whether strain can be used to assign treatments that lead to improved cardiac function and are eventually associated with a reduction in HF.
Preserving Ovarian Function During Chemotherapy And Old Age
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
Chemotherapy treatment and the natural ageing process leads to ovarian failure and infertility. For young cancer survivors, chemotherapy induced infertility is devastating, and like aged women, leads to hormonal changes that lead to osteoporosis, diabetes, obesity, and neurodegeneration. Here, a new class of molecules will be tested for their ability to prevent and reverse infertility folllowing chemotherapy treatment, and in old age. These findings will improve the healthy lifespan of women.