Cancer

The Australian Genomics ‘SUPER WGS’ Flagship is investigating the use of whole genome sequencing to better profile complex cases of Cancers of Unknown Primary (CUP). The researchers hope to be the first to investigate the use of whole genome sequencing for CUP.

Cancer of Unknown Primary (CUP) describes when a cancer has spread (‘metastasised’) but the starting point of the cancer (the ‘primary tumour’) cannot be located despite many diagnostic investigations.

CUP is challenging to treat and clinical care varies widely in Australia because there are no guidelines to direct the management of patients with CUP.

The integration of modern molecular assays into standard care is needed to improve outcomes for those with CUP and to guide future clinical trial research.

This Flagship builds on an existing cohort study called SUPER (‘Solving Unknown Primary CancER’) funded by Cancer Australia and the Victorian Cancer Agency. The study was established to investigate ways to improve outcomes in CUP patients through the use of molecular profiling, including DNA panel sequencing and gene-expression based site-of-origin predictive tests, called ‘SUPERDx’.

The SUPER study is also exploring the unmet needs of patients with CUP and assessing the economic impact of molecular profiling methods for CUP. Clinicians providing care to CUP patients are also being surveyed to report the impact of molecular profiling on individual patient care.

The SUPER WGS has recently received a $5m boost from the Australian Government’s Medical Research Future Fund to continue its work under the ‘SUPER-NEXT’ study. Read more about SUPER-NEXT here.

Lung cancer is the most common cause of cancer death in Australia. More than 11,500 people are diagnosed each year, with about 30 per cent surviving just one year.

Recent discoveries have demonstrated some patients benefit from therapy that targets certain genetic changes in their cancer cells. While current genetic testing approaches lead to about 15 per cent of lung cancer patients gaining benefit from these targeted therapies, this Flagship study aims to better these outcomes by using improved methods for cancer tissue collection, and more comprehensive approaches to genetic testing.

The Australian Genomics Lung Cancer Flagship builds on an existing research project funded by the QIMR Berghofer Medical Research Institute, Cancer Council Queensland and Cancer Australia that aims to improve the collection of cancer tissue for primary diagnoses and genetic testing using a reliable and highly-sensitive technique called Endobronchial Ultrasound Transbronchial Needle Aspiration (EBUS-TBNA).

The Flagship is expanding on this study to investigate the use of genomic testing (using whole exome sequencing and whole genome sequencing) following EBUS-TBNA in an effort to identify not only the small number of genetic changes currently tested for, but to potentially reveal all the different genetic changes that are present in the cancer.

The researchers hope that EBUS-TBNA and genomic testing will lead to better diagnostic approaches and identify a wider spectrum of genetic changes in lung cancer tissue that could be treated with new targeted therapies in the future.

There are 300 new cases of Acute Lymphoblastic Leukaemia (ALL) each year, affecting both children (~60% of all diagnoses) and adults. ALL is the largest cause of non-traumatic death in children, and many adults with ALL will die of their disease.

A number of recent genomic discoveries, that have the potential to improve outcomes for ALL patients, have been made using next generation genomic sequencing.  Many of these genomic alterations are potentially targetable with drugs that we currently have. Importantly patients with these genomic changes are not readily identified, using current diagnostic approaches.

Australian Genomics is working with a number of leukaemia researchers and clinicians around Australia to improve the outcomes of ALL patients. We work with the leading clinical trialist networks in the country, interacting with adult haematologists through the Australasian Leukaemia and Lymphoma Group (ALLG), and paediatric haemato-oncologists through the Australian and New Zealand Children’s Haematology/Oncology Group (ANZCHOG). Through these networks, we provide access to genomic testing for patients with ALL, and foster collaborations between clinicians and researchers.

Our goal is to develop a diagnostic pipeline in a clinical setting, to allow timely intervention using precision medicine approaches with the ultimate aim of improving outcomes for our patients. The project will also enable evaluation of the cost benefit of these approaches, particularly with respect to clinical outcomes (disease free and overall survival), and also compare quality of life outcomes between current and these future approaches.

Solid tumours are growths of cancerous cells that can occur in many parts of the body and genomic sequencing of these cells can identify specific genetic changes within an individual’s cancer that are driving this growth.

This shared project with Melbourne Genomics Health Alliance is examining the clinical impact of a complex genomic sequencing program in advanced solid cancers in Australia as well as investigating the genomic testing experience from both patient and clinician perspectives.

Our goals are to enhance clinical trial participation and expand treatment options for patients through molecular profiling of a wide range of cancer types including a paediatric cohort, and focussed groups of lung, melanoma and rare cancers.

In addition to modelling the impact of large panel sequencing versus current standard of care testing, the cost/benefit of the personalised medicine approach will be evaluated, as well as analysis of clinical and laboratory processes to inform practices for efficient and patient focussed genomic testing advanced cancer patients in the future.

The ICCon Partnership is a Cancer Council NSW-funded national collaboration of Familial Cancer Centres, research groups and consumer advocates focused on hereditary cancer syndromes.

Empirical observations at Familial Cancer Centres across Australia reveal many families with unusual clusters of cancers, or individuals with multiple primary cancers, often occurring at an early age. Such observations point toward the likelihood of a hereditary cancer syndrome. Hereditary (or ‘familial’) cancers are caused by the presence of one or more ‘gene variants’ that increase the risk of cancer. These gene variants are present from birth and are usually inherited from a parent. Individuals with such an inherited gene variant have a 50 per cent chance of passing it to each of their children.

The rapid evolution in genomic technology means that an adoption of a whole genome approach to germline genetic testing is fast approaching. However, this needs to be tested in the clinical environment to ensure its adoption is useful, safe and cost efficient. Furthermore, to integrate whole genome sequencing into routine clinical practice it needs to be ensured that the necessary infrastructure is in place.

In this Flagship we are working with families with a suspected familial cancer syndrome where previous routine genetic testing has not provided a diagnosis. For each affected cancer patient we are creating a report of possibly clinically actionable variants identified in a panel of 107 genes known to cause familial cancers, and discussing with the treating clinics the potential consequences of these variants for the affected families.

A further research component analyses the entire genome. We are developing sequence analysis methods to identify structural changes that would impact the function of known hereditary cancer genes, and we are also looking for variants impacting genes not yet known to play a role in hereditary cancers. If considered relevant, findings from this research component and the potential consequences for the affected families will be discussed with the clinics.