The 3-dimensional Structure Of Anticancer Drug-DNA Complexes Determined By X-ray Crystallography
Funder
National Health and Medical Research Council
Funding Amount
$264,358.00
Summary
Our main objective is to discover the molecular details of how cancer drugs interact with DNA and how these interactions differ from those of inactive chemically related compounds. We propose to use X-ray crystallography together with the successful methods we have developed for determining the 3-dimensional structures of the DNA complexes of a class of antitumour active drugs to study the complexes of other clinically or scientifically important DNA intercalating anticancer drugs. These agents ....Our main objective is to discover the molecular details of how cancer drugs interact with DNA and how these interactions differ from those of inactive chemically related compounds. We propose to use X-ray crystallography together with the successful methods we have developed for determining the 3-dimensional structures of the DNA complexes of a class of antitumour active drugs to study the complexes of other clinically or scientifically important DNA intercalating anticancer drugs. These agents act by poisoning the DNA binding enzyme topoisomerase. Crystallographic analysis will give us unequivocal answers at the atomic level as to the exact way in which the drug binds to DNA and how this binding differs between antitumour active and inactive compounds. We believe that a knowledge of the DNA binding mode of a class of intercalating anticancer drugs at the atomic level is valuable in guiding drug design within that class.Read moreRead less
Novel Precision-based Treatments For Biliary Tract Cancer
Funder
National Health and Medical Research Council
Funding Amount
$644,241.00
Summary
Advanced biliary tract cancer has a median life-expectancy of ~12 months. The relatively low incidence of the disease in Australia requires a collaborative team-based approach to drive progress. To achieve this, we have established a multidisciplinary research team based in Australia, Thailand and Japan. Here, we will now build on our exciting preliminary discoveries to test new patient-specific treatments, and develop methods to efficiently identify patients who may respond to immunotherapy.
A Randomized Trial Of Idarubicin Dose Escalation In Consolidation Therapy For Adult Acute Myeloid Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$425,000.00
Summary
This project is a clinical trial to test the value of giving a higher than usual dose of one of the most important anti-cancer drugs, called idarubicin, in the initial treatment of adults with newly diagnosed acute myeloid leukemia (AML). This disease is the most serious form of leukemia in adults, and is usually treated with strong anti-cancer drugs, including idarubicin. Research in Australia and overseas has shown that increasing the doses of the other major drug (called cytarabine) used to t ....This project is a clinical trial to test the value of giving a higher than usual dose of one of the most important anti-cancer drugs, called idarubicin, in the initial treatment of adults with newly diagnosed acute myeloid leukemia (AML). This disease is the most serious form of leukemia in adults, and is usually treated with strong anti-cancer drugs, including idarubicin. Research in Australia and overseas has shown that increasing the doses of the other major drug (called cytarabine) used to treat AML in adults results in a doubling of the number of people cured of this disease, given that they have achieved a remission. This project will examine whether there is a similar benefit of increasing the idarubicin dose beyond that which has been conventionally used up to date. People who have AML diagnosed at one of the Australian hospitals participating in this study will receive initial treatment with an established drug combination. Those patients achieving a good response to the first treatment will then be randomly allocated to receive 2 further courses of treatment, one with a conventional dose of idarubicin, and the other with double the idarubicin dose. All patients will then be assesed for side effects of the treatment, and followed for at least 3 years for any signs of recurrence of their leukemia.Read moreRead less
The Use Of Real-World Evidence To Support Regulatory And Reimbursement Decisions
Funder
National Health and Medical Research Council
Funding Amount
$91,538.00
Summary
Traditionally, medicines are studied extensively in clinical trials before they are widely available. More recently, some medicines have been allowed to enter the market without complete data on their benefits and risks. This means that these issues can only be studied once a medicine is on the market and used in routine clinical practice; this is referred to as real-world evidence. This research evaluates if this evidence is sufficient to prove that a medicine is safe and that it works
We recently discovered a new way to treat melanoma by inhibiting a protein called MDM4 that is important in promoting tumor growth in ~2/3 of melanomas. In this proposal, we will extend this work to see if anti-MDM4 therapy is effective in laboratory models that are more relevant to patients and in combination with other melanoma therapies. We will also explore additional ways of inhibiting MDM4 that may make anti-MDM4 therapy even more potent.
The blood-brain barrier is a major impediment to the treatment of brain tumours because it prevents most anti-cancer drugs from entering the brain, and brain tumour, from the bloodstream. This proposal examines new approaches to open the blood-brain barrier to allow the use of existing highly potent anti-cancer drugs as brain cancer therapies. Successful outcomes of this work could lead to substantial improvements in the outcomes for brain tumour patients.
Developing Novel Agents To Prevent Tumour Recurrence In Glioblastoma
Funder
National Health and Medical Research Council
Funding Amount
$1,089,561.00
Summary
Glioblastoma is a form of brain cancer that is currently incurable. We have discovered that switching-off an enzyme called KDM4 (using 'KDM4 inhibitors') improves chemotherapy outcomes with new drugs also discovered in our laboratory. This project will examine a novel drug combination treatment for glioblastoma patients and generate evidence for initiation of clinical trials. This could initiate a novel therapy that could significantly extend patients' lives.
Apoptosis And Stem/Progenitor Cells In The Development And Treatment Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$21,809,604.00
Summary
To improve cancer therapy, we are studying two cancer hallmarks. The first is excessive cell survival. To combat this, we are developing drugs with commercial partners that directly activate the cell's death machinery. The second hallmark is inexorable proliferation, akin to that of stem cells, which can generate entire tissues, as we showed for the breast. ‘Rogue’ stem-like cells may initiate certain cancers. We hope to advance cancer therapy by identifying such cells and drugs that kill them.
Development Of Novel And Selective Anticancer Drugs Derived From Cysteine.
Funder
National Health and Medical Research Council
Funding Amount
$264,250.00
Summary
In the next few years cancer is projected to become the leading cause of death in industrialised countries. Cancer chemotherapy currently relies on destruction of tumours by toxic drugs that indiscriminately kill all cell types, resulting in side effects that limit treatment. In the 21st century new cancer drugs will more effectively destroy malignant tumour cells without damaging normal cells. The R and D herein will value-add to our discovery of a new class of potent and orally active anti-tum ....In the next few years cancer is projected to become the leading cause of death in industrialised countries. Cancer chemotherapy currently relies on destruction of tumours by toxic drugs that indiscriminately kill all cell types, resulting in side effects that limit treatment. In the 21st century new cancer drugs will more effectively destroy malignant tumour cells without damaging normal cells. The R and D herein will value-add to our discovery of a new class of potent and orally active anti-tumour drugs that possess unusually high selectivity in acting on cancer cells without killing normal human cells. Our current proof of concept will be turned into a drug development candidate that will improve our negotiating position with commercial partners.Read moreRead less