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Understanding and targeting prostate cancer metabolism

South Australian medical researchers have identified a new way in which prostate cancer cells use glucose to grow and survive, which in turn could be the secret to destroying them.

In a new study published in the international journal eLife, researchers from SAHMRI, Flinders University and the University of Adelaide used cutting-edge technologies to analyse this metabolic pathway in prostate cancer cells, demonstrating that it represents a weakness in prostate tumours that could be exploited to develop new therapies.

Associate Professor Luke Selth from the Flinders Health and Medical Research Institute (FHMRI) and Freemasons Centre for Male Health and Wellbeing (FCMHW) at Flinders University says the study provides important insights into how prostate tumours change their metabolism to enable rapid growth and resistance to therapies.

“Prostate cancer cells are very different to normal prostate cells in many ways but one of the most striking differences is how tumours use sugars and fats for energy production and to rapidly grow. In this study, we found that a protein called 6PGD can support the survival of prostate cancer cells when they are being challenged with a hormonal therapy that is currently used in the clinic”.

The study found that switching on 6PGD enables the cancer cells to use glucose for the generation of antioxidants and to make the building blocks for growth.

“We think this is a significant finding because it potentially represents a new mechanism by which prostate cancer cells can become resistant to hormonal therapies, which are the standard-of-care treatment for men with advanced and metastatic disease”, says Selth.

Co-lead author Professor Lisa Butler, from SAHMRI and the University of Adelaide, says the results are a step forward in understanding the unique metabolism of prostate tumours.

“Using the latest technologies, we generated an incredibly detailed view of how 6PGD influences prostate cancer metabolism. Importantly, our work has pinpointed some clinical agents that may be able to shut down this pathway, so it is possible that our findings could eventually be used to develop a new targeted therapy for this common disease”, says Butler.

The study showed that 6PGD inhibitors could kill cancer cells grown in lab dishes and even in real tumours taken directly from Adelaide cancer patients, and these inhibitors were more effective when combined with a hormonal therapy.

This story was originally published on the SAHMRI website. ACRF has backed $4.3 million of brilliant research at SAHMRI.

Industry support to probe fundamental questions in cancer

A new “tumour barcoding” technique known as SPLINTR, developed at the Peter MacCallum Cancer Centre, will be applied to common variants of non-small cell lung cancer.

SPLINTR can identify and track over time patterns of gene expression that give certain tumour cells an advantage, helping them to become dominant within a cancer.

Tumour samples of specific lung cancers will be analysed this way, both before and after patients are treated with targeted drugs.

Professor Mark Dawson, whose lab led the development of SPLINTR, said the research could open a new window on the gene expression underpinning this cancer, and drivers of treatment resistance.

“We are excited to collaborate with Pfizer in this early-stage research which may point to new ways to extend treatment responses, and improve outcomes, for lung cancer patients,” Professor Dawson said.

This project will also involve significant contributions from Peter Mac’s Professor Ben Solomon, Associate Professor Jayesh Desai and Professor Sarah-Jane Dawson.

Professor Ricky Johnstone, Executive Director Cancer Research at Peter Mac, said it was fantastic to see industry providing direct support for early-stage research.

“We are delighted that Pfizer – through its Emerging Science Fund – is helping to address really important and fundamental questions in cancer as this is how we drive the development of new diagnostic and treatment options for our patients,” he said.

“Pfizer’s Emerging Science Fund is an important resource for fulfilling our purpose to work across the healthcare ecosystem to translate science and technologies into medicines and vaccines that improve patients’ lives,” said Barbara Sosnowski, Vice President and Global Head Emerging Science & Innovation Leads at Pfizer.

“As a company with a long history of dedication to lung cancer patients, we are pleased to support the team at Peter Mac in this early-stage program.”

This story was originally published on the Peter Mac website. ACRF has backed $9 million of brilliant research at Peter Mac.

New DNA-based test on the horizon for children with solid tumours

When an Australian child is diagnosed with the blood cancer, acute lymphoblastic leukaemia (ALL), the treating clinician is almost certain to make use of an important DNA-based technique called ‘minimal residual disease testing’ to help guide treatment decisions. But for children diagnosed with solid tumours, no such test is available.

New Australian research, led by scientists at Children’s Cancer Institute published this month in the British Journal of Cancer, brings us one step closer to having such a tool.

The research shows that the new technology of whole genome sequencing (WGS) can be used to identify tumour-specific ‘markers’ − gene alterations unique to an individual patient – which can, in turn, be used to measure cancer levels in that patient’s body at different points in time. Specifically, the markers allow the detection of ‘minimal residual disease’ (MRD): cancer cells that have survived treatment and will lead to relapse, if allowed to do so.

MRD testing has proven to be a game-changer for children with ALL, helping clinicians monitor disease progression and treatment response, and enabling the early detection of relapse. Now, it is hoped that the same can be done for children with solid tumours.

To investigate the feasibility of using WGS technology as the basis of MRD testing for solid tumours, the researchers used data from the Zero Childhood Cancer Program (ZERO), Australia’s first personalised medicine program for children with cancer, which involves extensive molecular testing and analysis of children’s tumours, including WGS. Since the program began in 2015, it has generated unprecedented data about cancer in children, including previously unavailable genomic data.

According to lead researcher, Dr Toby Trahair, Clinical Research Fellow at Children’s Cancer Institute, and paediatric oncologist at the Kids Cancer Centre, Sydney Children’s Hospital, it is the availability of this data that has opened the door to developing an MRD test for children with solid tumours.

“Progress in developing this kind of test has been hampered by a lack of necessary data,” he explains. “Because of the whole gene sequencing done through ZERO, we now have access to information we simply didn’t have before. What we’ve done for this study is investigate whether we can use that data for the purpose of MRD testing in children with solid tumours.”

Specifically, the study asked whether identifying tumour-specific gene sequences using WGS can lead to an accurate and reliable way of detecting and measuring MRD in a patient’s bone marrow and peripheral blood. According to its findings, the answer to that question is Yes. And while their research focused on high-risk neuroblastoma and Ewing sarcoma, the authors believe the findings are likely to be applicable to multiple types of cancer.

The clinical implications of the findings will need to be explored in prospective clinical trials. However, Dr Trahair is optimistic. “In the ZERO national clinical trial [2017-2020], the average time it took to generate detailed genomic data for a patient was just over 7 weeks. A validated MRD assay can be developed and applied within 6 weeks of receiving genomic data. This means it would be feasible to provide real-time MRD results for a child with high-risk neuroblastoma or Ewing sarcoma from mid-induction therapy onwards. That’s very exciting, because it means those MRD results have the potential to change the outcome for that child.”

This work was made possible by funding from Children’s Cancer Foundation, Australia and the funding partners of the Zero Childhood Cancer Program.

This story was originally published on the Children’s Cancer Institute website. ACRF has backed $9.6 million of brilliant research at Children’s Cancer Institute.

New slide technology lights up early-stage breast cancer

An innovative microscope slide – NanoMslide – is promising to revolutionise medical imaging after researchers demonstrated that it could be used to detect breast cancer cells in patients.

The technology was developed at La Trobe University by Professor Brian Abbey and co-inventor Dr Eugeniu Balaur, who then teamed up with Associate Professor Belinda Parker’s group at the Peter MacCallum Cancer Centre to trial it as an aid to diagnosing very early-stage breast cancer.

In their study published today in Nature, they demonstrate that by modifying the surface of conventional microscope slides at the nanoscale, biological structures and cells take on a striking colour contrast which can be used to instantly detect disease.

“Current approaches to tissue imaging often rely on staining or labelling cells in order to render them visible under the microscope,” Professor Abbey said.

“Even with staining or labelling, it can be challenging for pathologists to detect cancer cells, with the risk that some samples are misdiagnosed, particularly during the very early stages of disease.

“Recent breakthroughs in nanotechnology have allowed us to manipulate the interaction of light with biological tissue so that abnormal cells appear to have a different colour to healthy ones. Comparing images from our slides to conventional staining is like watching colour television when all you’ve seen before is black and white.”

Associate Professor Parker said current techniques can mean it is difficult to distinguish early forms of breast cancer from benign lesions, particularly when there are not many abnormally-shaped cells in a complex tissue.

The NanoMslide makes such a diagnosis much easier.

“When I first looked at a tissue under the microscope on the NanoMslide, I was incredibly excited,” said Associate Professor Parker, who is also an adjunct associate professor at La Trobe.

“For the first time I saw cancer cells just popping up at me. They were a different colour from the surrounding tissue, and it was very easy to distinguish them from surrounding cells.”

Associate Professor Parker believes the NanoMslide will complement existing stains currently in use, to allow for more consistent cancer diagnoses.

“Based on our preliminary findings with the NanoMslide, we think this platform could be really useful in early breast cancer diagnosis, but also in other cancers where we’re really just trying to pick up a few cancer cells in a complex tissue or a blood sample.”

The study was conducted in collaboration with Professor Sandra O’Toole from the Garvan Institute of Medical Research who was the lead pathologist, and clinical and research partners at the Royal Melbourne Hospital, the Olivia Newton‐John Cancer Research Institute, The University of Melbourne and the Australian National University.

Professor Abbey’s group were able to develop their slide technology by harnessing open access equipment and expertise made available by the Melbourne Centre for Nanofabrication, the flagship facility of the Victorian node of the Australian National Fabrication Facility (ANFF-VIC).

This story was originally published on the Peter Mac website. ACRF has backed $9 million of brilliant research at Peter Mac.

World-first 3D imaging for melanoma detection

Queenslanders could have skin cancer diagnosed earlier using world-first 3D scanning technology with the launch of the Australian Cancer Research Foundation Australian Centre of Excellence in Melanoma Imaging and Diagnosis.

University of Queensland Dermatologist Professor H. Peter Soyer said the technology enabled researchers to track moles and skin spots over time using full body mapping, making it a game-changer for melanoma detection.

“This technology is revolutionising early melanoma detection using 3D state-of-the-art body imaging systems that take an image in milliseconds,” Professor Soyer said.

“The telemedicine network allows dermatologists and medical professionals to detect skin cancers remotely, even from the other side of the country.

“For the first time, medical researchers can access a national database of up to 100,000 patient images taken by 3D full body imaging systems located in Queensland, NSW and Victoria, as part of the world’s largest melanoma imaging trial, which aims to develop more efficient and effective screening for the early detection of skin cancer.   

“Using algorithms created by artificial intelligence, the 3D imaging systems are able to analyse the images and produce a full body skin spot map, which transforms the way we will monitor patients in the future.”

Australia has the highest rates of melanoma in the world with an average 28,000 Australians diagnosed with the disease every year.

ACRF chief executive officer Kerry Strydom said the Australian Cancer Research Foundation backed the best in research and cutting-edge technology to drive innovation and help create the new Centre.

“Melanoma is a deadly problem that needs disruptive solutions, and ACRF is proud to be to be involved in delivering revolutionary research through this pioneering program,” Mr Strydom said.

The project brings together three leading Australian universities in skin research, UQ, The University of Sydney and Melbourne’s Monash University, to form the interconnected Centre of Excellence in Diagnostic Imaging of Early Melanoma.

Queenslanders can sign up here to be part of the world’s largest melanoma imaging trial using the 3D full body imaging system located at Brisbane’s Princess Alexandra Hospital.

This blogpost originally appeared on The University of Queensland (UQ) Website. ACRF has backed $16.4 million of brilliant research at UQ.