Major achievements in cancer research

Cancer researchers at the University of Sydney have done ground-breaking research. We list here some of their more recent achievements.

Clinical practice guidelines for communicating prognosis and end-of-life issues

Researchers at the University of Sydney have developed new guidelines for communicating prognosis and end-of-life issues. The guidelines are for all members of the health care team who care for patients with advanced life limiting illnesses and their families.

Prognosis, prediction of the course of disease and whether or when it might cause death, is an issue that most doctors and patients describe as difficult to discuss. Expert opinion about communicating prognosis and other matters relating to the end-of-life varies and there is limited high quality evidence on how best to discuss them with patients and caregivers.

To address these issues, guidelines were developed by University of Sydney researchers Dr Josephine Clayton, Dr Karen Hancock, Professor Phyllis Butow and Professor Martin Tattersall, in collaboration with Professor David Currow from Flinders University. The guidelines were launched by the National Health and Medical Research Council in 2007 and have been formally endorsed by many organisations, including the Australian and New Zealand Society of Palliative Medicine, the Australasian Chapter of Palliative Medicine (Royal Australian College of Physicians), Cancer Voices Australia and Palliative Care Australia.

Two communication skills training modules for Medical Staff have been developed based on the content of the guidelines, one for Palliative Medicine Advanced Trainees and Specialists and one for hospital resident medical officers. The Australasian Chapter of Palliative Medicine and the Royal Australasian College of Physicians developed the first in collaboration with international communication skills training experts from the United States; it was launched in December 2008. The second, a brief individualised communication skills training module, is currently being piloted at Royal North Shore Hospital by Dr Clayton, Professor Butow, Dr Fran Boyle and Professor Tattersall, in collaboration with the Pam McLean Communication Centre.

A NHMRC Strategic Palliative Care Research Grant has supported this research. Dr Clayton received a Cancer Institute NSW Career Development and Support Fellowship and a Clinical Research Fellowship, which enabled her to research palliative care while continuing to practise Palliative Medicine.

Clayton JM, Hancock KM, Butow PN, Tattersall MHN, Currow DC. Clinical practice guidelines for communicating prognosis and end-of-life issues with adults in the advanced stages of a life-limiting illness, and their caregivers. Medical Journal of Australia 2007; 186 (12): S77- 108. This publication can be downloaded for free from Medical Journal of Australia website.

How much is too much? A breakthrough in cancer treatment

Radiation treatment administered to patients with prostate cancer will be significantly safer and more effective due to a novel medical sensor developed by scientists at The University of Sydney. For the first time, doctors will be able to determine and administer the maximum safe dose of radiation.

In a unique research collaboration combining radiation medical physics, optical fibre technology and oncology, researchers have created an Optical Fibre Dosimeter, a tiny optical fibre (one millimetre in diameter) with a scintillator – a miniature bead that absorbs particle radiation. The fibre is threaded into the patient via an existing catheter allowing doctors to measure the radiation dose as it is being received.

The Fibre Optic Dosimeter was developed by a multidisciplinary team of experts: Professor David McKenzie, Doctoral student Jamil Lambert, Associate Professor Natalka Suchowerska and Dr Michael Jackson from the Sydney Cancer Centre, and Professor Simon Fleming and Dr Sue Law, from the University’s Optical Fibre Technology Centre. The researchers collaborated to develop the fundamental science underpinning the technology with the support of an ARC Linkage Grant and later received a NSW Cancer Council Project Grant to develop the specific clinical application.

Radiation treatments used currently by doctors rely on estimates of optimal radiation exposure. Too much radiation can compromise the quality of life of cancer patients by causing unnecessary side effects, while too little radiation may fail to cure the cancer. In prostate cancer patients, excessive radiation can cause urethral complications such as pain and trouble urinating. However, it is difficult to avoid high dose radiation to the urethra as it passes through the prostate gland. The Optical Fibre Dosimeter will enable doctors to measure the optimal dose of radiation, and will indicate whether the radiation is hitting the right spot.

The researchers’ industry partners, Bandwidth Foundry and CMS Alphatech, have formed a spin-off company, Radiant LX, with the assistance of Anna Grocholsky from Sydnovate, the University’s IP management office. With the support of a NSW Cancer Council grant, the research has recently entered clinical trials at Royal Prince Alfred Hospital.

In a new phase of the study, funded by an NHMRC project grant, the researchers will build a prototype Fibre Optic Dosimeter array to measure the radiation dose to the rectal wall (which is also very sensitive to some radiation treatments). While the present study focuses on prostate cancer treatment, fibre optic dosimeter technology may have clinical applications in the treatment of other cancers.

Switching on the light: The identification of a core cancer enzyme

Ground-breaking research conducted by scientists at the Children’s Medical Research Institute will significantly advance research into cancer and anti-cancer treatments, through the identification of the composition of human telomerase, an enzyme vital to the maintenance of many cancers.

Since its discovery 18 years ago, the protein composition of telomerase has been unknown. A study, conducted by Dr Scott Cohen of the Children’s Medical Research Institute, revealed that telomerase contains just 2 proteins. ‘Until now, researchers studying telomerase have not been sure what they were working with,’ said Dr Cohen, whose research was supported by The Cancer Council NSW and the National Health and Medical Research Council Australia, and published by leading journal Science.

Dr Cohen developed an elegant technique to purify human telomerase to facilitate the identification of its composition. ‘No-one has previously been able to purify telomerase because, within each cell, it’s a very rare enzyme. Each cell has about 20 molecules of telomerase – compared to about 20 million molecules each of some abundant enzymes,’ said Dr Cohen. ‘I had to pull out one part in 100 million, which is roughly a teacup of water from an Olympic swimming pool.’

These findings will significantly enhance the ability of cancer researchers to further study telomerase. Dr Roger Reddel, Director of CMRI and an international cancer research expert, believes the identification ‘switches on a light’ for basic cell biology and cancer research. ‘Telomerase is the target of an extensive global effort to develop anti-cancer treatments. This discovery sharpens the focus of these efforts and no doubt will speed up the process of delivering successful treatment,’ said Dr Reddel.

Dr Cohen’s identification of the composition of telomerase creates possibilities to further study human telomerase using research methods such as x-ray crystallography, which will be a major step towards the identification of new anti-cancer drugs.

The impact of calcium intake and vitamin D status on the care of breast cancer patients

Dr Colin Dunstan and his research group at the ANZAC Research Institute (Professor Markus Seibel; Dr Yu Zheng; Li Laine Ooi; Dr Hong Zhou) are at the forefront of investigating the relationships between the bone micro-environment and the growth of breast cancer cells. They study the behaviour of human breast cancer cells (MCF-7 and MDA-MB-231) that are injected to target, or are already growing in, the bones of “nude” mice; mice that have a defective immune response. They then change the bone environment and observe how this affects the cancer cells’ ability to settle or grow in bones.

These researchers have found that inhibiting bone resorption (with osteoprotegerin, a natural decoy receptor for RANK ligand, or ibandronate, a bisphosphonate antiresorptive, inhibits the growth of breast cancer cells in bone, both by decreasing their proliferation and increasing their apoptosis (programmed cell death). These effects appeared to be due to decreases in the activity of osteoclasts (cells naturally involved in bone resorption) and not to direct effects on cancer cells.

In contrast, when bone resorption was increased by feeding a low calcium diet, growth of the cancer cells increased. This effect was blocked by treatment with osteoprotegerin, suggesting that changes in bone cell activity also mediated the effect of a low calcium diet.

Since many patients with cancer have increased bone resorption due to a low calcium intake or relative vitamin D insufficiency, evaluation and correction of calcium and vitamin D insufficiency may be of value in the care of breast cancer patients.

Identifying your target: The development of DotScan

In 1998, two researchers from the University of Sydney were frustrated that chemotherapy, with its serious side-effects, was the best treatment available for a friend who had been diagnosed with acute myeloid leukaemia (AML).

Professors Richard Christopherson and Cris dos Remedios developed the concept that an extensive repertoire of proteins expressed on the surface of a patient’s leukaemia cells could enable rapid diagnosis of the type of leukaemia and a strategy for more specific treatment, by identifying potential targets for therapeutic antibodies.

This concept lead to the development of DotScan – a solid-phase cell-capture assay using an antibody microarray to immunophenotype cancer cells. The University of Sydney formed a start-up company, Medsaic Pty Ltd, to develop DotScan in 2003. DotScan is a specialised product for the diagnosis of blood cancers, solid tissue tumours and autoimmune diseases. It is based on cell capture by microarrays of antibodies bound to nitrocellulose-coated microscope slides. The system consists of a microscope slide dotted with an array of specific antibodies that capture cells, an array reader to record the pattern of cell binding, and software to interpret the binding pattern that can provide a diagnosis.

Flow cytometry is currently the gold standard for identifying a limited number (10-15) surface molecules as one of 5 or 6 criteria used for diagnosis. DotScan provides an extensive profile of surface antigens (147) enabling diagnosis of leukaemias and lymphomas based solely upon their surface profiles at lower cost. DotScan will provide a better understanding of a patient's condition and better treatment as a consequence. The antibody microarray is available as a kit in Australia and has been assigned a Medicare rebate item number. It is the first in a suite of tests under development that also includes microarrays for profiling solid tumours (Prof Christopherson) and autoimmune diseases (Prof dos Remedios).

Medsaic Pty Limited ACN: 094 771 141. Suite 145, National Innovation Centre, Australian Technology Park, Garden Street, Eveleigh, Sydney, NSW 1430 Australia. Ph: +61 2 9209 4445. Fx: +61 2 9209 4646.

Establishment of the Breast Cancer Tissue Bank

The establishment of the Breast Cancer Tissue Bank (BCTB) is a great step forward for breast cancer research in Australia. The bank is being led by Associate Professor Clarke from the University of Sydney at the Westmead Institute of Cancer Research, and a team of investigators from around NSW, including University of Sydney affiliates Drs. Rosemary Balleine and Debbie Marsh, Professors Rick Kefford and Rob Baxter, and Associate Professors Paul Harnett, Michael Bilous and John Boyages.

The Bank has been created to provide a resource of breast cancer biospecimens and clinical data to support breast cancer research throughout Australia. It is supported by a collaborative network of cancer clinicians and researchers across NSW and the ACT, who cooperate to provide samples and information from breast cancer patients for use in research.

With funding from the NHMRC, Cancer Institute NSW and the National Breast Cancer Foundation, the BCTB is building a large collection of breast cancer specimens and information about women with breast cancer that can be used for future research. The Breast Cancer Tissue Bank consists of a collection of samples of breast cancer and normal breast tissue, as well as blood samples which are taken from women diagnosed with breast cancer together with some information about the health and breast cancer treatment and outcome of donors. Materials in the bank are processed and stored using international best practice methodologies to preserve the integrity of the specimens and increase their value to research scientists.

A number of collections centres across NSW have been established to recruit donors to the bank under the oversight of the BCTB Project Manager, Ms Jane Carpenter. Currently there are six collection centres located at Royal Prince Alfred Hospital, Westmead Hospital, Kolling Institute, St Vincent's Hospital, John Hunter Hospital and a regional centre in Port Macquarie. Two additional sites will commence in early 2009 based in the ACT and at Liverpool Hospital.

Access to human tissue is essential for translating current research knowledge into clinical practice and in turn basic researchers can utilise information derived from human specimens to drive further investigation into the molecular basis of disease.

For more information, please visit the Breast Cancer Tissue Bank website.