Changing the way we treat skin cancer

Researchers at the Illawarra Health and Medical Research Institute are leading a multi-institutional research project to better understand and treat squamous cell carcinoma (SCC) of the skin, one of the most common skin cancers in Australia.

Thanks to three-year funding from the National Health and Medical Research Council, IHMRI’s Senior Professor Marie Ranson and Associate Professor Bruce Ashford, who are leading the project, are investigating molecular changes of the cancer to determine what causes it to spread.

“SCC of the skin is so common amongst Australians, but we still don’t know why some tumours spread to nearby lymph nodes and why others do not,” Senior Professor Ranson said.

“Our aim is to decipher the molecular changes that distinguish those SCCs that are likely to spread so that clinicians can identify and treat these patients early.”

Senior Professor Marie Ranson

A better prognosis, more targeted treatments

The project aims to achieve better prognosis and more targeted treatments for one of Australia’s most common cancers and major healthcare burdens.

Patients with aggressive variants of cutaneous SCC often present late, when the cancer has already spread through lymphatics to nodes in the neck.

“When patients present at such a late stage, we have to treat with both radical surgery and high dose radiotherapy. Even then, the chances of surviving beyond five years are only about 50%,” A/Professor Ashford explained.

“We want to be able to identify whether there are early markers that distinguish whether we can avoid unnecessary surgery, or whether we should use even more aggressive treatment.”

Associate Professor Bruce Ashford

Understanding the genetic landscape

Senior Professor Ranson, A/Professor Ashford and the IHMRI team are unravelling the genetic landscape of SCC through the process of whole genome sequencing. Through this process, researchers can see if there is a signature within these tumours that can help predict which ones will spread.

“If we find a signature, it will enable clinicians to more accurately identify at-risk patients to diagnose and treat metastatic SCC early. We have so far completed whole genome sequencing on 33 patient specimens and are completing RNA sequencing of these tumours,” Senior Professor Ranson explained.

The tumour samples are collected from surgery at both Wollongong Hospital and the Chris O’Brien Lifehouse in Sydney. Whole genome sequencing works by comparing cancer cells to normal cells to check for mutations in the DNA. If researchers can find a common pattern of mutation within the cancers, it will help identify which tumours will spread.

“Over three years we hope to examine between 60 and 80 patient specimens. This grant also helps fund the employment of bioinformaticians to help us understand the complex nature of DNA variation in this deadly disease,” said Senior Professor Ranson.

The project is a collaboration with partners, Associate Professor Ruta Gupta from Royal Prince Alfred Hospital, and Professor Narayanan Gopalakrishna Iyer from the National Cancer Centre in Singapore.

Protecting children receiving chemotherapy from hearing loss

Researchers at Ear Science Institute Australia have developed a novel nano-gel therapy to protect children receiving chemotherapy from hearing loss – a common side effect of the cancer treatment.

The project which involves testing the nano-gel in a new study is led out of Ear Science Institute Australia and supported by funding from the Channel 7 Telethon Trust.

A much-needed preventative approach

Lead researcher, Associate Professor Hani Al-Salami, said about half of children who go through chemotherapy will have some degree of permanent hearing loss due to toxicity of the drugs.

“There is currently no proven prevention or cure for this hearing loss, so this new research will test the effectiveness of a nano-gel that is injected into the ear before chemotherapy to prevent the possible side effect of cancer treatment among children,” Associate Professor Al-Salami explained.

“The nano-gel has been developed in partnership with Curtin University by a group of clinicians, pharmaceutical scientists, ENT (ear, nose and throat) surgeons, cochlea physiologists and synthetic chemists using cutting-edge technologies.

“Human bile extract is put through specialised systems to produce a gel, which is capable of being injected into the human ear. It can potentially protect children from the side effects of chemotherapy, which targets and destroys cancer tissues and can also kill other healthy tissues resulting in problems including hearing loss.”

Associate Professor Hani Al-Salami in the lab
Associate Professor Hani Al-Salami in the lab

Looking forward

Ear Science Institute Australia CEO, Sandra Bellekom, said it was a very exciting time for ear and hearing medical research in Western Australia.

“The Telethon grant will allow Ear Science to further develop an established and proven nano-gel, improving efficacy and making it safer for use in our children,” Ms Bellekom said.

The Channel 7 Telethon Trust’s support of Ear Science Institute Australia also includes funding for the procurement of a newly developed scanning electron microscope for use in the research, which is capable of micro and nano scale visualisation of critical features of the nano-gel.

Predicting relapse in children with cancer

Research at Children’s Cancer Institute has already led to a highly accurate test to predict relapse in children with leukaemia. Now, an equivalent test for children with solid tumours is on the horizon.

Testing for ‘minimal residual disease’

When an Australian child is diagnosed with the blood cancer, acute lymphoblastic leukaemia (ALL), their doctor is almost certain to make use of a DNA-based technique called minimal residual disease (MRD) testing. The test works by detecting and measuring the level of leukaemia cells that remain in the child’s body after treatment begins, and is a powerful predictor of relapse. But for children diagnosed with solid tumours, no such test is available − yet.

‘The key to identifying children at high risk of relapse is to be able to detect even the tiniest quantities of minimal residual disease, as early on in their treatment as possible,’ explained Professor Murray Norris AM, who led the team that developed molecular technology so sensitive it is capable of detecting one leukaemic cell in a million normal cells.

‘This gives the child’s doctor an opportunity to alter treatment well before relapse occurs.’

Professor Norris

When tested in clinical trials, the Institute’s MRD technology led to an effective doubling in survival rates in children with high-risk ALL, and it now underpins tailored treatment strategies for children diagnosed with ALL throughout Australia.

Developing an MRD test for solid tumours

Recent research, published in the British Journal of Cancer, suggests we are getting close to having the equivalent of an MRD test available for children with solid tumours.

Led by Dr Toby Trahair, Clinical Research Fellow at Children’s Cancer Institute and paediatric oncologist at the Kids Cancer Centre, Sydney Children’s Hospital, the research shows that whole genome sequencing (WGS) technology can be used to identify tumour-specific markers, which can be used to detect cancer cells that have survived treatment and will lead to relapse if allowed to do so.

‘To find out if we could use WGS technology as the basis of MRD testing for solid tumours, we looked at data from the Zero Childhood Cancer Program (ZERO), Australia’s first personalised medicine program for children with cancer,’ explained Dr Trahair.

‘ZERO involves extensive molecular analysis of children’s tumours, including WGS, and has given us access to the kind of data we’ve never had before.’

Dr Trahair

‘Our results strongly suggest that using WGS to identify tumour-specific gene sequences is going to lead to a very accurate and reliable way of detecting and measuring MRD in children with solid cancers. And while our research focused on high-risk neuroblastoma and Ewing sarcoma, we believe the findings are likely to be applicable to multiple types of cancer.’

Improving pain relief for patients with advanced cancers

A trans-national clinical trial, involving Peter Mac patients, has found stereotactic ablative body radiation therapy (SABR) provides superior relief from painful spinal lesions than standard radiation therapy.

The SC24 phase II/III trial – which involved patients in Canada and Australia – showed SABR was effective both for more patients, and for longer, at relieving the pain caused by secondary tumours in the spine.

Pain is a quality of life issue

Associate Professor Shankar Siva said the findings were practice-changing and would lead to improved quality of life for many patients with advanced cancers in need of pain relief.

“We know that up to 40% of patients with solid cancers will develop secondaries in the spine – across many different types of cancer – and back pain is a major issue for quality of life,” said Associate Professor Siva, who led the trial in Australia in behalf of the Trans Tasman Radiation Oncology Group (TROG Cancer Research).

“Conventional radiation therapy for pain relief is the current standard-of-care. This trial has shown that SABR – as an advanced form of this treatment – leads to even better pain relief which is more durable than standard radiation therapy.”

A more precise and targeted option

SABR is more precise and targeted than standard radiation therapy, and involves delivering higher doses of radiation across fewer treatment sessions.

After three months, 35% of participants randomised to the trial’s SABR arm reported no remaining pain from their treated spinal lesions, compared to 14% who received standard radiation therapy. After six months, 32% in the SABR arm reported no pain compared to 16%.

The trial was coordinated by the Canadian Cancer Trials Group at Queen’s University in collaboration with the Study Chair, Dr Arjun Sahgal, Cancer Ablation Program Director at Sunnybrook Health Sciences Centre in Toronto. Associate Professor Siva was awarded a National Health and Medical Research Council (NHMRC) grant to conduct the study across Australia through TROG Cancer Research, with Peter Mac as the lead site.

The trial results are published in the journal Lancet Oncology.

Team effort drives stomach cancer discoveries

Understanding how stomach cancer develops and progresses to invasive stages could lead to much-needed, better treatments.

Pinpointing the culprits

More than 2000 Australians are diagnosed with stomach cancer each year. Sadly most cases are detected at late stages when treatment options are limited.

A team led by WEHI researchers, Dr Lorraine O’Reilly and Dr Tracy Putoczki, investigated signalling molecules that may contribute to stomach cancer.

They focused on inflammatory signalling, as there is a clear link between inflammation and stomach cancer, as explained by Dr O’Reilly.

“Using a laboratory model of stomach cancer that we had developed, we measured the amounts of different inflammatory signalling molecules – called cytokines – to see which were present in stomach cancers as they developed and progressed. This revealed high levels of four key cytokines,” she said.

The next stage of the research was to inhibit these cytokines, and measure the impact on stomach cancer progression, said Dr Putoczki.

“We discovered that removing a cytokine called TNF could prevent early-stage stomach cancers from progressing to a more severe stage that, in humans, is much harder to treat,” she said.

“This was an exciting finding, as there are already medicines in clinical use that block TNF, most notably for the treatment of rheumatoid arthritis.”

“Our research suggests these therapies could be an effective and safe way to prevent the progression of stomach cancer to more invasive forms.”

Dr Lorraine O’Reilly

Boosted by consumer involvement

The involvement of research consumers – people who have lived experience of stomach cancer – was critical to the success of the research, Dr O’Reilly said.

“We valued the input of stomach cancer survivor Mr Frank Graham and his wife Ronnie, as well as Mrs Debra Clements, who nursed her husband through cancer. They conveyed to me the importance of considering current issues for cancer patients, such as early diagnosis and more effective targeted treatments. Their feedback helped me to refine the study design,” she said.

Dr Lorraine O’Reilly Senior Postdoctoral Fellow (Silke Laboratory, Inflammation Division) Mr Frank Graham (stomach cancer survivor)

Dr O’Reilly also consulted with consumers about her application for research funding. “Debra, Frank and Ronnie provided invaluable feedback on my grant application, helping me to successfully secure the essential support I needed to continue my research,” she said.

Mr Graham said that volunteering as a consumer at WEHI had changed his perspective on medical research.

“It’s my sincere hope that one day other people won’t have to go through what I’ve been through,” he said.

“I am incredibly optimistic about the future knowing there are people like Lorraine working behind the scenes to improve medical treatments and longer-term positive outcomes for people with stomach cancer.”

Mr Frank Graham

NatureBank – facilitating natural product drug discovery from Australian flora and fauna

NatureBank is a unique biodiscovery platform derived from Australian plants, fungi and marine invertebrates that enables researchers to do ground-breaking biodiscovery research. This platform has yielded some exciting discoveries, including a promising compound active against prostate cancer.

In Australia, we are lucky to be surrounded by some of the most unique and diverse animal and plant species in the world. This cornucopia of biodiversity has the potential to lead us to new medicines for a range of diseases. Nearly half of all current medicines worldwide are derived from nature. Examples include aspirin, which is based on a compound found in the bark and leaves of the willow tree; the anticancer compounds vinblastine and vincristine from the rosy periwinkle plant for the treatment of leukemia and Hodgkin’s disease; paclitaxel from the Pacific Yew tree for treatment of breast, ovarian, prostate and lung cancers; and many more human and animal treatments.

NatureBank – a unique Australian biodiscovery resource

But how can we tap into Australia’s biodiversity to discover new medicines? The answer is NatureBank – a unique biodiscovery platform derived from Australian plants, fungi and marine invertebrates that enables researchers to do ground-breaking biodiscovery research (https://www.griffith.edu.au/institute-drug-discovery/unique-resources/naturebank).

Housed within the Griffith Institute for Drug Discovery (GRIDD) in Queensland, Australia, NatureBank is Australia’s largest biodiscovery resource. It contains > 30,000 archived flora and fauna samples, a > 21,000 extract library and a > 105,000 fraction library. These libraries represent the unique biodiversity of Australia, which translates into novel chemical diversity.

NatureBank is a legacy from a $100M investment (1994-2007) from AstraZeneca to Griffith University’s now Griffith Institute for Drug Discovery. This was the largest pharma research partnership investment made to an Australian organisation at the time.

NatureBank accelerates biodiscovery by providing researchers (academic and industry) with access to samples containing compounds with high potential for development into new drugs, animal health products, agrichemicals, food ingredients or additives, nutraceuticals, cosmeceuticals and other industry applications. The NatureBank libraries have been shared with more than 30 universities, research institutes and companies.

Associate Professor Rohan Davis, the academic lead of NatureBank, based at the Griffith Institute for Drug Discovery. Picture: Nigel Hallett

From NatureBank to an exciting candidate to treat prostate cancer

One of these collaborations has recently transitioned to the next exciting stage that could lead to the development of a new pharmaceutical drug targeting prostate cancer. Prostate cancer is the second most common cancer diagnosed in Australian men and the third most common cause of cancer death. By the age of 85, one in six men will be diagnosed with prostate cancer. As such there is an urgent and unmet need to discover and develop new treatments for this prevalent disease.

Back in 2014, Dr Michelle Liberio and Associate Professor Rohan Davis of GRIDD screened marine-derived samples from NatureBank against a prostate cancer cell line. This led to the discovery and isolation of a promising compound from a sea squirt sample that was collected from the Great Barrier Reef.  A synthetic method was then developed to access larger quantities of the compound. In 2021, this compound progressed to animal testing in prostate cancer models through a collaboration with Professor Colleen Nelson and Dr Jennifer Gunter of the Australian Prostate Cancer Research Centre, Queensland University of Technology and the Translational Research Institute at Princess Alexandra Hospital.

“NatureBank is a truly unique biodiscovery resource that has enabled us to discover new molecules from Nature that affect cancer metabolism. These compounds have the potential to impact cancer drug discovery and development.”

Professor Colleen Nelson, Queensland University of Technology

This is a major step in the translation of this compound into a pharmaceutical drug. By accessing NatureBank, the research team were able to accelerate the first stages of the discovery pipeline – identifying a significant compound with activity against prostate cancer from the millions of possible compounds in various screening libraries. Over a number of years, the research team have utilised a collaborative approach across institutes to progress this promising compound towards the ultimate goal of helping save the lives of men diagnosed with prostate cancer.

In order to progress this discovery towards a lifesaving treatment for prostate cancer patients, the research team will continue to seek investment to obtain their goal. One thing is for sure though, NatureBank significantly contributed to the acceleration of the first stages of this discovery.

“Without access to NatureBank, and the wonderfully unique chemistry it contains, we would never have discovered this marine-derived natural compound. NatureBank is a treasure trove of riches that is waiting to be used by scientists for the discovery and development of not only new anti-cancer drugs, but also other natural chemicals that might be used to fight infections, neurological conditions and other human diseases”- Associate Professor Rohan Davis, GRIDD.

With NatureBank having such high potential to be a source of not only new drugs but also, for example, animal health products, agrichemicals, food ingredients or additives, nutraceuticals, and cosmeceuticals, we are sure to see more promising candidates emerge from this unique biodiversity platform in the future.

Associate Professor Rohan Davis explain the uniqueness of NatureBank:

Banner image: Photo courtesy of the Queensland Museum