Cancer

Currently the major hurdle facing the successful treatment of solid cancers is the development of metastases (tumour spread), and our lack of understanding of what controls this process.

Neuro Oncology is a niche area with around 500 newly diagnosed GLioma patients per year in NSW; however the care and support needs for this patient group are great, with high carer burden. 

By inhibiting a key player in the DNA repair pathway we could improve the effectiveness of chemotherapeutic treatments.

Aim 1: Confirmation of ERCC1 biomaker of chemoresistance; Aim 2: Investigate the epigenome of ovarian cancer extreme responders and non-responders to platinum chemotherapy

A good quality of life and long survival are standard societal expectations of health care, but sadly this is not the norm for patients with brain cancer (glioma). Surgery, radiotherapy, and chemotherapy are current therapies which target cancer cells directly but have shown limited benefit to patients long-term.

The CN2 will provide expert clinical consultancy to support high level care coordination for brain cancer patients requiring complex management.

A very useful and convenient method used in many fields of medical research involves growing cells in the laboratory. Cells are ""cultured"" in plastic dishes in incubators that provide an environment warmed to body temperature, 37 degrees Celsius. Human cells also require carbon dioxide to grow and this is added to the ambient air in the incubator. This kind of cell culture has been used for over a century and has been accepted as the standard way of growing cells in the laboratory. This method is very important and useful in cancer research.

Ovarian cancer is usually treated with a chemotherapy drug called cisplatin which works by damaging DNA so much that the tumour cells die. Cisplatin is used to treat a wide variety of tumours in addition to ovarian cancer including, testicular, head and neck and non-small cell lung cancer. In addition, it forms the basis of most combined treatment regimes (where 2 or more drugs are used in combination). The downside to cisplatin is that it is extremely toxic and although some patients benefit substantially from treatment, a large proportion suffer the toxic side effects without any therapeutic benefit. We are aiming to develop a personal test to determine if cisplatin is likely to be effective for an individual’s ovarian cancer, so that the toxic side effects can be avoided if the drug is not going to work.

Childhood brain tumours (CBTs) are the second most common paediatric malignancy after leukaemia and the leading cause of cancer-related death in children under the age of 19 years. CBTs can be classified into several distinct groups based on their cell morphology and malignant potential. All CBTs have a neuroepithelial origin and are thought to be derived from neural stem cells that can differentiate into a variety of different tumour types such as astrocytic tumours, oligodendroglial tumours, mixed gliomas, ependymal tumours, neuronal and mixed tumours, neuronal and glial tumours, embryonal tumours and primitive neuroectodermal tumours. By far the most frequent are gliomas, followed by embryonal tumours. 

Shwachman-Diamond-Syndrome (SDS) is an inherited disease that affects 1 in every 76,000 children. Dysfunction of the child’s blood and circulatory system occurs in nearly all patients, causing increased rates of infection and decreased capacity to transport oxygen. Unfortunately, the overall survival of a young person with SDS is only 35 years, and this is attributed to sepsis, organ failure and most frequently the development of leukaemia. 

Recent discoveries, including from our laboratory, have revealed the important role played by nerves in cancer progression, and targeting nerve outgrowth in the tumour microenvironment is an emerging innovative strategy in oncology. In pancreatic cancer, it has been shown that the outgrowth of sensory nerves in the microenvironment is necessary to cancer progression and stimulates pain.

Faecal occult blood testing (FOBT) is used as a population based method to identify people over the age of 50 years with colorectal cancer.   Fortunately, the majority of patients with a positive FOBT do not have colorectal cancer and only about 5% are diagnosed with CRC and 30% with polyps after colonoscopy.  Colonoscopy is not without risk and even in the most experienced hands there is a morbidity associated with this procedure.

Cancer is the most common cause of childhood disease-related deaths, with leukaemia the most common childhood cancer in Australia. The two most common forms of leukaemia in children are acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Whilst remission is achievable in over 95% of ALL cases, 1/3 of patients will relapse within 5 to 10 years, and these children will not be long-term survivors. AML accounts for 20% of all childhood leukaemias, and the outlook for children diagnosed with AML is much worse, with only approximately half of children surviving for 5 years post-diagnosis.

This is a versatile, automated platform for quantification and quality control of DNA, RNA and proteins. It can process up to 16 samples in less than two minutes. This instrument does not require cleaning action so there are no chances of contamination from remnants of RNA from the previous sample. Once loaded the sample remains saved up to two hours as there is no evaporation loss. This machine provides the option for flexible input & multi-sample read. The analysis is automatic and a digital report is generated which can be exported to a USB. 

The Role of Tumour Microenvironment in Ovarian Cancer

Understanding and overcoming treatment resistance in brain tumours

Brain cancer is one of the most under researched of all cancers, little is known about its cause or how to treat it, resulting in very low survival rates. Brain cancer research increasingly relies on collections of tumour samples and associated data (biobanks). Due to the location of brain cancer, and its rare nature, obtaining sufficient clinical samples is difficult. Furthermore, brain cancer biobanks across Australia are geographically and operationally disparate, and to date there has been no effort to coordinate them.

Metastatic pancreatic cancer has a low survival rate and even with the best existing therapies the survival is less than a year. Despite advances in treatments and outcomes for other cancers, this has not happened for pancreatic cancer with no advances in mortality reduction observed over the past decade. This grim outlook drives our research, which focuses on developing novel diagnostic strategies for pancreatic cancer.

The Bioimpedence Scales are essentially a pair of 'fancy' scales that measure the density of body tissue to predict body mass - amount and composition. This is important because we know the relative amounts of fat and lean tissue in a patient affect how much of a drug gets to a particular site like the tumour and also determines how long it stays there and how the drug is released over time.

The QX200 AutoDG Droplet Digital PCR System will increase the genomic research capacity of HMRI helping researchers to understand the molecular basis of the disease.

Annually there are 2,000 new cases of brain cancer in Australia. Prognosis for people with brain cancer is dire. It is the highest cause of death in 0-39 age group with a 5-year survival rate of 19%. Brain cancer results in 5,000 hospitalisations per year (average stay 12.5 days, the longest of any cancer) and has the highest lifetime cost per patient of $1.89m [1].

AML (acute myeloid leukemia) is a very aggressive form of leukemia. Tumour suppressor proteins are critically important for normal healthy cells to be protected from genetic mutations. However in AML mutations occur in the genes responsible for stem growth and cell differentiation.

Annually there are 2,000 new cases of brain cancer in Australia. Prognosis for people with brain cancer is dire. It is the highest cause of death in 0-39 age group with a 5-year survival rate of 19%. Brain cancer results in 5,000 hospitalisations per year (average stay 12.5 days, the longest of any cancer) and has the highest lifetime cost per patient of $1.89m.

To develop a test for predicting ovarian cancer response/resistance to cisplatin chemotherapy that can be quickly implemented in clincial centres.

Matt will use his Jennie Thomas medical research travel grant to attend the European Molecular Biology Organisation (EMBO) Targeted Proteomics Course to be held at the Centre for Genomic Regulation, Barcelona, Spain where he will learn the theory and methods necessary to implement targeted proteomics workflow on patient samples which he will then pass onto the researchers of HMRI.
 

More than 3,000 women die of breast cancer each year in Australia.

Acute myeloid leukaemia (AML) is the most common acute leukaemia affecting adults, and accounts for ~20% of childhood leukaemias.

While a diagnosis of a brain tumour is devastating and life-changing, low grade brain tumours initially have a relatively slow moving clinical course and good prognosis.

Dr Craig Gedye will use his Mark Hughes Foundation Travel Grant to join top national and international researchers at the COGNO (Co-operative Trials Group for Neuro-Oncology) meeting in Brisbane.

Funding is requested to attend the Inaugural International Cancer Immunotherapy Conference, September 16 -19, 2015, in New York, New York, USA. 

Pia Laegdsgaard will use her Mark Hughes Foundation travel grant to present at the COGNO Annual Scientific Meeting in Brisbane this month. Pia has developed a research poster outlining the processes involved in establishing and managing the brain cancer facility as part of the HCB.

Whilst treatments for brain cancer are improving these do not work well in all patients. 

The 65th Annual Meeting of the American Society of Human Genetics (ASHG) 2015, Baltimore, MD, USA (6-10 October 2015)
 

Prostate cancer is the most commonly diagnosed cancer in men in Australia. Once a prostate cancer begins to spread (metastasise), it becomes very difficult to treat and often results in patient death. 

The aim of this research is to understand how diabetes cause complications in other parts of the body.

Shwachman-Diamond Syndrome (SDS) is an inherited condition affecting bone marrow, the pancreas, skeletal system, and other organ systems. 

Pancreatic Cancer is the fourth leading cause of cancer related death in the western world and there is an urgent need to develop new therapeutic strategies. 

Whilst treatments for brain cancer are improving these do not work well in all patients.

Prostate cancer is a common male malignancy that can be difficult to accurately diagnose and to determine its grade, so that the best treatment can be provided.

Currently the major hurdle facing the successful treatment of solid cancers is the development of metastases (tumour spread), and our lack of understanding of what controls this process.

Ovarian cancer is usually treated with a chemotherapy drug called cisplatin which works by damaging DNA so much that the tumour cells die.

Hsin-Yi currently has a postdoctoral position at the Melanoma Research Laboratory of the Cancer Program at HMRI.

Improving survival from Acute myeloid leukaemia (AML) with new therapies

A new treatment for acute myeloid leukaemia

A new target for melanoma treatment 

Fluoropyrimidines (5-FU and capecitabine) are anticancer drugs commonly used in a range of cancers including oesophageal, gastric and colorectal cancers.  Their toxicity is unpredictable, leading to significant and sometimes life-threatening side effects.  Pharmacokinetics (steady state plasma level, area under the curve, etc.) varies between patients by a factor of 5-10, and this is also unpredictable.  Although therapeutic drug monitoring might allow better management of pharmacokinetic variability by rapid dose adjustment, it is labour-intensive and time-consuming.

Androgen suppression (AS) used prior to or following RT for locally advanced prostate cancer reduces cancerous recurrence in the prostate and at metastatic sites, thereby also reducing prostate cancer mortality. 

Breast cancer is the most common malignancy that develops in women, responsible for the highest cancer-related death rates. While the prognosis is good if the cancer is limited to the breast; once a patient has developed metastatic disease they are essentially incurable.