Understanding How Second Primary Malignancies Arise Following Multiple Myeloma Therapy
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Multiple myeloma is a cancer of white blood cells. Chemotherapy and new drugs that target cancer cells are the most effective therapies for multiple myeloma. However, these drugs also increase the chance of developing a secondary cancer that is different to the initial cancer. Little is known about how these cancers arise. I aim to find out how current therapies cause secondary cancers; with the hope of finding alternative therapies for multiple myeloma that do not cause secondary cancers.
A New Strategy To Prevent Anthracycline-induced Cardiotoxicity While Improving Anti-cancer Activity
Funder
National Health and Medical Research Council
Funding Amount
$318,034.00
Summary
The anthracycline-based drugs such as doxorubicin currently used for cancer treatment have a major side effect in that they induce heart damage. We have shown that doxorubicin action can be modified to result in greater tumour cell kill, but also with reduced death of cardiac cells. We now aim to develop a molecular understanding of this process in order to allow better design of chemotherapy regimes that include the anthracyclines.
Rational Design And Development Of New Anthracenedione Derivatives
Funder
National Health and Medical Research Council
Funding Amount
$471,702.00
Summary
Our laboratory has discovered a way to activate the anti-cancer drug mitoxantrone to make it bind to DNA more effectively. This involves pre-activating it with the simple molecule formaldehyde. This concept has enabled us to design new anticancer drugs that are predicted to be more effective at killing cancer cells. In this study we will synthesise these new compounds then test how effectively they bind to DNA, inhibit growth of tumour cells in culture, and inhibit growth of tumours in mice.
Dietary Protein-induced DNA Damage In Colon And Consequences For Colorectal Oncogenesis
Funder
National Health and Medical Research Council
Funding Amount
$604,797.00
Summary
This research will explore the effects of dietary protein on genetic damage to cells lining the large bowel and risk of developing colorectal cancer. We will determine the degree and type of DNA damage resulting from increased protein, the cellular response to this DNA damage, whether it increases risk for developing bowel cancer and whether it can be minimised by other foods in both an animal model and humans.
Regulation Of Mutational Load By Chemopreventive Agents And Implications For Molecular Pathogenesis Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$423,750.00
Summary
In Australia colorectal cancer is the second most common cause of cancer death, however the morbidity and mortality of colorectal cancer is currently not under control. Identification of safe and practical preventive agents should aid control. There is increasing evidence that colorectal cancer is associated with endogenous (internall) and exogenous (external) factors. They cause damage to DNA which might lead to tumour development if the damage is not repaired. This study will first identify th ....In Australia colorectal cancer is the second most common cause of cancer death, however the morbidity and mortality of colorectal cancer is currently not under control. Identification of safe and practical preventive agents should aid control. There is increasing evidence that colorectal cancer is associated with endogenous (internall) and exogenous (external) factors. They cause damage to DNA which might lead to tumour development if the damage is not repaired. This study will first identify the ability of preventive agents (aspirin-like drugs, fish oil, and antioxidants) to regulate DNA damage, then examine the effect of combination of the agents. It will finally determine the ability of agents, or combination of agents, to prevent development of colorectal cancer using two animal models. Prevention of human CRC by such a strategy should be feasible. First, evidence indicates that DNA damage is important in tumour initiation. Second, exogenous regulation of DNA damage, repair and removal seems possible. Epidemiological studies have suggested that that 30-70% of cancer can potentially be prevented with proper adjustment of diets (fat, fibre, resistant starch) and supplements of drugs (NSAIDs) or antioxidants (Vitamin, Selenium). Third, preventive strategies are likely to be feasible. At the population level, they would need to be safe and manageable in the context of dietary lifestyle, but this can be achieved through a range of food technology developments. In individuals at high risk, personalised preventive strategies become feasible through doctor-patient contact. This study focuses on regulation of DNA damage, and its repair and removal during the early stage of tumour development. The study will provide information if preventive agents, alone or in combination, provide a promising strategy for colorectal cancer through reduction of genetic damage. They might also identify new biomarkers that facilitate testing in humans.Read moreRead less
Development Of DNA Phosphate Crosslinking Agents As Potential Anticancer Drugs
Funder
National Health and Medical Research Council
Funding Amount
$392,545.00
Summary
The principal difficulty in the treatment of the common solid tumours that cause the majority of cancer deaths is the problem of drug resistance. For example, many patients with cancer of the lung, breast or colon respond well to drug treatment with their tumours initially regressing, only to return later in an aggressive drug-resistant form. In this event, the inevitable outcome is that the tumour grows through drug treatment and the patient eventually succumbs and dies. This is also a familiar ....The principal difficulty in the treatment of the common solid tumours that cause the majority of cancer deaths is the problem of drug resistance. For example, many patients with cancer of the lung, breast or colon respond well to drug treatment with their tumours initially regressing, only to return later in an aggressive drug-resistant form. In this event, the inevitable outcome is that the tumour grows through drug treatment and the patient eventually succumbs and dies. This is also a familiar scenario in the treatment of adults with leukaemias and non-Hodgkins lymphomas. The underlying cause of drug resistance is the genetic instability of cancer cells which results in tumours that are heterogeneous, making it almost inevitable that a cancer cell will arise that is resistant to treatment. There are many mechanisms of resistance, some of which are peculiar to particular drug types, some are permeability barriers and some involve genetic deregulation of the biochemistry of cell death. Alkylating agents are one of the most important classes of anticancer drug. They bind irreversibly to the bases in DNA and weld the two strands of the double helix together. This cross-link is a powerful block to DNA replication and leads to the death of cancer cells by the process of programmed cell death. Cancer cells generally become resistant to alkylating agents by invoking repair mechanisms that remove the drug from the DNA bases, a response which breaks the cross-link and returns the DNA to its normal state. In this project, we are developing a new type of alkylating agent that reacts not with the DNA bases but with the phosphate groups of the DNA backbone. By this means the strands of DNA can again be cross-linked but now the linkage is between parts of the DNA that cancer cells cannot separate. In this way, we hope to be able to devise new drugs that are resistant to the normal mechanisms of DNA repair so that they will be active against drug-resistant tumours.Read moreRead less