‘Catch-22’ Scenario Good News for Some Cancer Patients

Image above: (from left to right) Bachelor of Science student Gavin Turrell, UQ Research Fellow Dr Meihua Yu, Dr Janin Chandra, Professor Ian Frazer, and UQ Research Fellow Dr Ahmed Mehdi.

Traits that allow cancer cells to escape the body’s natural defence system and develop into tumours are actually a good indicator to a patient’s survival prognosis, according to University of Queensland researchers.

UQ Diamantina Institute researcher Dr Janin Chandra described the discovery as a “catch-22 situation” and good news for patients with either cervical or head and neck cancer who have immune inhibitory traits present in their tumours.

“Our natural defence system is programmed to pick up abnormal cancerous cells and destroy them before they can grow into a tumour mass and spread through our bodies,” Dr Chandra said.

“However, the tumour can grow by developing cunning strategies to either escape our natural defence system, or to actively block it.

“We call these strategies immune inhibition, and until recently we thought this trait was a bad thing.

“Our recent research has shown that tumours of patients with either cervical cancer or head and neck cancer which had many immune inhibition traits, had the best five-year survival prognosis compared to patients with tumours without the traits.”

The data also showed that tumours with immune inhibition traits also had high levels of defence system activity, which fight against cancer.

Dr Chandra said researchers now had a better understanding that having immune inhibition traits in the tumour was actually not bad, and in fact was a sign of immune activation.

People who lack this immune activity inside the tumour, regardless if ‘good’ or ‘bad’ immune activity, have a worse prognosis.

She said this knowledge had important implications in designing future therapies for cancer.

“On average only 20 percent of patients respond to new immune-targeted drugs, so we are organising a clinical research study to develop predictors of response to these drugs,” Dr Chandra said.

“You need to give patients that aren’t responding to treatment an alternative, so our research is geared to identify new targets that could be used for patients who don’t have any natural defence cells in their tumours.”

Image above: (from left to right) Bachelor of Science student Gavin Turrell, UQ Research Fellow Dr Meihua Yu, Dr Janin Chandra, Professor Ian Frazer, and UQ Research Fellow Dr Ahmed Mehdi.

The research paper – Immune-inhibitory gene expression is positively correlated with overall immune activity and predicts increased survival probability of cervical cancer patients – is published in Frontiers in Molecular Biosciences Molecular Diagnostics and Therapeutics (DOI: 10.3389/fmolb.2021.622643).

This story originally appeared on the UQ Diamantina Institute website.

ACRF has awarded five grants to the UQ Diamantina Institute, including the initial seed funding for the development of a vaccine to prevent cervical cancer.

Dual drug approach to treat deadly melanoma

Research from the Centenary Institute has found that a new dual drug approach could offer up a highly effective treatment strategy for melanoma, the most serious form of skin cancer responsible for more than 1,700 deaths each year in Australia.

Reported in the ‘Journal of Investigative Dermatology’ the findings have the potential to benefit melanoma patients who do not respond favourably to current therapeutic treatments.

In the study, the research team found that the combined use of inhibitors targeting two specific proteins markedly reduced the growth of melanoma both in cellular experiments as well in models with mice. The two proteins targeted were the bromodomain and extra-terminal domain (BET) family of proteins and cyclin-dependent kinase 9 (CDK9). High expression of BET and CDK9 proteins are associated with an adverse prognosis in melanoma patients and also regulate melanoma cellular activity.

According to Dr Abdullah Al Emran (pictured) , researcher in the Melanoma Oncology and Immunology Program at the Centenary Institute and lead author of the study, a key finding from the study was that the combination BET and CDK9 inhibitor treatment demonstrated significantly increased melanoma killing benefits when compared to use of the same inhibitor drugs when tested alone.

“Co-targeting BET and CDK9 proteins with inhibitors killed high numbers of melanoma cells regardless of type or status including melanomas exhibiting both BRAF and NRAS genetic mutations. The inhibitors worked by disrupting separate signalling pathways found within the melanoma cells–those responsible for cell communication and growth and this may explain the effectiveness we saw,” he said.

“We also found molecular gene signatures suggesting biomarkers of which melanoma patients were most likely to respond to this BET and CDK9 inhibitor treatment,” he added.

Dr Jessamy Tiffen, Head of the Centenary Institute’s Melanoma Epigenetics Laboratory and senior author on the research paper believes that use of combination drug treatments may offer up a new strategic approach in the fight against the often fatal skin cancer.

“Over half of all melanoma patients do not respond to current therapies and new treatment approaches are urgently required. We’ve now seen that drugs working in combination are able to produce a synergistic effect when it comes to the killing of melanoma cells. This strategy could lead to higher survival rates for patients and as a result we will be further exploring this exciting avenue of research,” she said.

This article originally appeared on the Centenary Institute Website.

In 2016, ACRF awarded at $2.5M grant to Centenary Institute for the establishment of the ACRF Tumour Metabolism Laboratory.

If you would like to financially support the work of ACRF please go to acrf.com.au/donate.

The ACRF Accelerate program

This week Australian Cancer Research Foundation has launched an exciting new initiative. The ACRF Accelerate program has been designed in line with our mission to reach a world without cancer. The program provides prospective donors with a unique philanthropic opportunity to evaluate and contribute towards promising cancer research projects. 

Survival rates from cancer are increasing thanks to decades of research, but around 396 Australians are still diagnosed with cancer every day. The Accelerate program connects generous donors who want to solve the problem of cancer with projects that have the ability to do just that.  

Tom Dery AO, ACRF’s Chair said: 

A year ago, we could never have imagined the world as it is today. From the devastation of fires and floods, through to a complete transformation in the way we connect, work, access healthcare, and travel. 

While the pandemic has highlighted the critical need for medical research into vaccine development, there also remains an ongoing need for investment in cancer research. That priority remains unchanged, and ever present.  

Despite improvements in patient outcomes, cancer continues to impact far too many lives. With vast economic pressures transforming the research funding environment, the work of Australian Cancer Research Foundation and the life-changing ACRF Accelerate program remains more vital than ever. 

Over the past 12 months, we’ve been inspired by the many generous Australians dedicated to supporting globally significant cancer research through our Accelerate program. We’re proud to say that groundbreaking, world-leading discoveries are happening right here in our own backyard because of their donations. 

As leaders in philanthropic investment, ACRF is committed to the rigour, review and assessment of the projects presented in the ACRF Accelerate program, providing you with confidence that every donation will result in real, measurable impacts for those living with cancer. 

On behalf of the ACRF board, I’m proud and excited about the potential opportunity this year’s ACRF Accelerate program presents to donors and researchers committed to changing the human and social impact of cancer in Australia. 

We invite you explore these innovative projects and consider a meaningful contribution towards their success. Find out more here: acrf.com.au/philanthropy

What is National Colorectal Cancer Awareness Month?

March is National Colorectal Cancer Awareness month. We’d like to take the opportunity to share information with you about colorectal cancer (or bowel cancer) in the hope that by raising awareness we can continue to reduce the number of people impacted by this type of cancer.

What is Colorectal Cancer Awareness month?

National Colorectal Cancer Month raises awareness for colorectal cancer, commonly known as bowel cancer. Colorectal Cancer Awareness month is an opportunity to learn more about this type of cancer and to share information including stories of those impacted by colorectal cancer. It’s also a time to support organisations, such as ACRF, working to equip researchers with the tools they need to improve the prevention, diagnosis and treatment of all types of cancer.

What is Colorectal Cancer?

Colorectal cancer is caused by the mutation of genes that cause cells in the large intestine to reproduce abnormally and form polyps. Most bowel polyps are not cancerous, but some polyps may become cancerous if left to grow into tumours. Colorectal cancer is also referred to as colon cancer or rectal cancer, depending on where it is found in the intestine. 

Colorectal cancer most commonly develops in the lower part of the descending colon, the sigmoid colon or rectum. More than 95 per cent of colorectal cancers are adenocarcinomas, cancers that start in cells forming the mucus-making glands that lubricate the colon and rectum. Other rare types include squamous cell cancers, Gastrointestinal stromal tumours, carcinoid tumours, sarcomas and lymphomas.

Colorectal Cancer facts In Australia

Colorectal Cancer is estimated to be the second most diagnosed type of cancer for both men and women and the third most common cause of death from cancer. It was estimated that over 15,000 Australians would be diagnosed with colorectal cancer in 2020.

When is Colorectal Cancer Awareness month?

March is National Colorectal Cancer Awareness month in the US and in Australia, June is Bowel Cancer Awareness Month.

How to create colorectal cancer awareness

Getting involved in Colorectal Cancer Awareness Month gives everyone the opportunity to make a difference. You can:

  • Wear a blue ribbon and encourage conversations about colorectal cancer.
  • Talk to family and friends about the realities of colorectal cancer, clearing up myths along the way.
  • Get tested regularly and encourage others to get tested too.
  • Post and share information about colorectal cancer on social media.
  • Support research into improving the prevention, diagnosis and treatment of all types of cancer, including colorectal cancer.

There are many ways to support the work of ACRF and together, with everyone’s input, we will achieve our goal to outsmart cancer. For more information on how you can support Colorectal cancer, learn how you can get involved with ACRF.

What is the Colorectal cancer awareness colour?

Blue is the colour for colorectal cancer awareness. Supporters are encouraged to wear blue clothes and/or blue ribbons to help spread awareness.

ACRF’s contribution to Colorectal cancer research

ACRF has partnered with several research institutes on initiatives to develop better prevention, earlier detection and more effective treatments for colorectal cancer. Some of these research initiatives include:

  • ACRF Centre for Integrated Cancer Systems Biology in South Australia. This state-of-the-art facility is utilising next generation technologies to transform patient outcomes through the delivery of targeted and personalised cancer therapy for a number of types of cancer including colorectal cancer.
  •  ACRF Breakthrough Technologies Laboratory to advance new treatments for many of Australia’s most common, and most deadly cancers, including colorectal cancer.
  • ACRF Centre for Therapeutic Target Discovery, potentially forming a scientific cornerstone of the first comprehensive cancer centre established in Australia. The centre created an innovative Australian-first collaborative and integrated cancer research centre, where clinicians, diagnosing and treating cancer patients, work closely with scientists researching the disease.

Spencer’s Story

This Colorectal Cancer awareness month we’d like to shout out to the heroes that continue to ensure ACRF can fund pioneering research to improve patient outcomes.

Loyal ACRF supporter Spencer Hird has supported bold cancer research by putting rubber to the road. He’s run Sydney’s City2Surf 47 times – even participating in the event virtually during COVID.

Sadly, Mr Hird lost his wife Heather in 1994 to bowel cancer. “I started fundraising soon after her passing and my focus has always been to give to cancer research. I am always impressed when I hear of improvements to treatments and diagnosis. It is so good to feel I might have contributed to that” says Mr Hird.

Thank you for your continued support Mr Hird.

Find out how you can support bold cancer research at acrf.com.au/get-involved

Steve’s Story

About 17 years ago, I shaved my head, moustache – and my legs! – to support a friend of mine, who sadly died from breast cancer. 

Around the same time, I had a spot removed from my back which turned out to be a stage 3 melanoma, so I had a large section removed from my back. I thought I was all good until 2017, when I found out that I had a secondary brain tumour. It was removed by the wonderful team at the Royal Brisbane Hospital. 

I was lucky enough to be one of the first people to trial immunotherapy for a year and had my thyroid removed late December 2019. I was in remission and going well until early February 2021, when I found out I had another brain tumour. This one had grown fast – from nothing in November 2020 to 20mm in February 2021. 

I will be undergoing a new treatment at the Princess Alexandra Hospital, called a Gamma Knife, which will shrink and kill the tumour. I will then undergo more immunotherapy to get rid of a couple of small tumours near my spine. 

Then I will be as good as new! Anything I can do to raise money to help is only a small thing compared to those who have done much more before me. Their support has allowed me to get the best and latest treatment to help me live a bit longer. 

I shaved my head and my moe for ACRF through the Hair Dare and raised $650. My youngest son Michael has taken on the dare too and I’m very proud of him. 

To learn more about how to shave, cut or colour for cancer research, head to shave.acrf.com.au

Terence’s Story

In late 2015 doctors found a mass growing in my brain after a routine check-up. After monitoring it for a few years, in late 2019 my neurosurgeon discovered that the mass was growing. Two thousand and twenty sucked for a lot of people but throwing in brain surgery and six months of chemo, all while a global pandemic was raging, wasn’t how I had pictured my wedding year!

I married my wife, Alyce, in February before my surgery – just before the lockdowns, so a win for us, I guess.  The year ended much better as we welcomed our son, Ryan, two weeks after chemo ended. He’s our number two, Emily, our daughter, is four. I take my hat off to Alyce for putting up with (I mean, supporting) me through treatment all the while going through pregnancy! Now THERE’S an inspiring story, but not mine…

One day during treatment, I got talking to an older lady who has been battling cancer for years and I was in awe of her positive attitude and bubbly personality. One thing she said that resonated with me was, “My dear, chemo is just the beginning… This journey living with cancer isn’t a sprint, as they say, it’s a marathon. The real challenges are up here,” as she pointed to her head.

So, that night, I decided that 12 months after I completed chemo, I was going to run a marathon. I completed chemo on 18 September 2020. The Blackmores Sydney Running Festival marathon is on the 19 September 2021. Fate perhaps? I’ve never been much of a runner, but why let fear stop me from doing something scary or different? I can’t change the fact that I have brain cancer. What I can change is the way I feel about it and to show those around me that cancer isn’t the GAME OVER moment some people fear it is. Why waste what life we have left in fear of things that could open our eyes to the world?

I’m running this marathon for me and all brain cancer warriors out there and also the people who dedicate their lives to overcoming all forms of cancer.

There are many ways to support the work of ACRF and together, with everyone’s input, we will achieve our goal to outsmart cancer. To find out more head to acrf.com.au/get-involved

Key steps discovered in production of critical immune cell

WEHI researchers have uncovered a process cells use to fight off infection and cancer that could pave the way for precision cancer immunotherapy treatment. 

Through gaining a better understanding of how this process works, researchers hope to be able to determine a way of tailoring immunotherapy to better fight cancer.

Led by Dr Dawn Lin and Dr Shalin Naik and published in Nature Cell Biology, the research provides new insight into the way cells adapt to fight infection.

Dr Shalin Naik and Dr Dawn Lin

This research lays the foundation for future studies into the body’s response to environmental stressors, such as injury, infection or cancer, at a single cell level.

At a glance

  • WEHI researchers have studied dendritic cells, a crucial component of the immune system, to gain a deeper understanding of how the body produces these cells to fight cancer and infection
  • The study found how the Flt3L hormone increased dendritic cells numbers
  • Researchers will now apply this knowledge to improving immunotherapy techniques to create more personalised treatments

Flt3L hormone plays vital role in fighting off infection

Dendritic cells are immune cells that activate ‘killer’ T cells, which are vital for clearing viral infections, such as COVID-19, but also for triggering a response to cancers such as melanoma and bowel cancer.

The Flt3L hormone can increase dendritic cell numbers, helping the immune system to fight off cancer and infection.

Dr Naik and his team studied developing immune cells at a single cell level to gain a deeper understanding of how the body uses these cells to trigger immune responses.

“There is one type of dendritic cell that the body uses to fight some infections and cancer. The Flt3L hormone increases numbers of this particular dendritic cell.”   

“We know quite well how the dendritic cell fights the cancer, but we don’t know how the Flt3L hormone increases the numbers of those dendritic cells,” he said  

Single-cell barcoding provides vital clues to how dendritic cells function

Researchers used a single-cell ‘barcoding’ technique to uncover what happened when dendritic cells multiplied.

“By using cellular barcoding – where we insert short synthetic DNA sequences, we call barcodes inside cells – we were able to determine which cells produced dendritic cells in pre-clinical models,” Dr Naik said.

“As a result of this research, we now better understand the actions of the Flt3L hormone that is currently used in cancer immunotherapy trials, and how it naturally helps the body fight cancer and infection. This is a first step to design better precision immunotherapy treatments for cancer.” 

Using single cell technology to improve immunotherapy treatment

This research answers a 50-year-long question as to what causes a stem cell to react in response to immense stress, such as infection or inflammation.

“We have known that the Flt3L hormone increases the number of dendritic cells for decades but now there is a focus on applying this knowledge to cancer immunotherapy and potentially to infection immunotherapy as well,” Dr Naik said.   

“The next stage in our research is to create ‘dendritic cell factories’ using our new knowledge, to produce millions to billions of these infection fighting cells and then use those in immunotherapy treatments.”

“These findings are a vital first step to improving immunotherapy treatments for patients, to help them better fight cancer and infection.”

WEHI authors

Dawn Lin, Luyi Tian, Sara Tomei, Daniela Amann-Zalcenstein, Tracey Baldwin, Tom Weber, Jaring Schreuder, Olivia Stonehouse, Samir Taoudi, Matthew Richie, Philip Hodgkin, Ashley Ng, Stephen Nutt, Shalin Naik.

This article originally appeared on the WEHI website. ACRF has awarded $10m in grants to WEHI for cancer research.

Our esteemed Medical Research Advisory Committee ensures that only the most promising cancer research initiatives in Australia receive our funding. If you would like to financially contribute, please go to acrf.com.au/donate

Microscopic behaviour of developing breast cells uncovered

An improved high-tech fluorescence microscopy technique is allowing researchers to film cells inside the breast as never seen before.

This new protocol provides detailed instructions on how to capture hi-res movies of cell movement, division and cooperation, in hard-to-reach regions of breast tissue.

The technology – called multiphoton microscopy – uses infrared lasers to illuminate fluorescently labelled breast cells without harming them, so that elusive cell behaviours can be observed within living tissue.

With the new method, WEHI researchers have revealed how breast cells rearrange, interact and sense their environment as the breast grows during development and recedes after lactation.

Cell imaging within living tissue has been achieved in many organs but the breast has remained especially challenging. So far, this new method has revealed exciting and unexpected details of breast biology and will help teams worldwide to advance research on breast development and cancer.

At a glance

An improved imaging protocol is allowing researchers to film cells as never seen before.

This new application of high-tech microscopy has enabled the imaging of stem cells as they guide breast development, and immune cells as they monitor the breast ducts to keep them healthy.

By imaging living, moving cells in their natural setting, researchers can better understand how our bodies function in real-time at the microscopic scale.

Understanding cell function

The protocol was developed by researcher Dr Caleb Dawson, in a team led by Professor Jane Visvader and Dr Anne Rios, in collaboration with Dr Scott Mueller from the Doherty Institute, and published in Nature Protocols today.

Dr Dawson said the filming technique unlocked a variety of applications to better understand how cells function, interact and develop.

“One of the most valuable things we have been able to film with the technique are the terminal end buds (TEBs) in breast tissue,” he said.

“These are club-like structures at the tips of the mammary ducts that grow during puberty to produce the branched tree structure of breast tissue. The unique cells inside the TEBs have never been filmed like this before so it was fascinating to watch this process for the first time.”

“We have watched a cell behaviour inside the TEB that was hypothesised in the 1980s but was never proven, and which has implications for breast stem cell function.”

Previously, TEBs had been studied by dissociating the individual cells and filming them outside the breast or by taking still images. With these approaches it is difficult to know how the cells actually behave and interact in living tissue.

“By filming the moving cells inside intact breast tissue in laboratory models, we are able to grasp a better understanding of how the cells behave and cooperate to help the breast to form and function properly.”

Dr Dawson said that he was grateful for the brilliant team and the cutting-edge technology provided by the Center for Dynamic Imaging at WEHI that made this work possible.

“When we embarked on our mission to film these processes, I had little knowledge of the effort it would require. With the vision of leading breast researchers Professor Visvader, Dr Rios and Professor Geoff Lindeman, alongside the live imaging expertise of Dr Mueller, and the microscopes available, we were able to achieve something that very few labs in the world have accomplished,” he said.

Opening the doors to new research opportunities

Dr Dawson said the filming technique could be applied to a host of research endeavours.

“Our approach enables us to image up to six fluorescent colours at the same time, which allows us to see how more cell types interact,” he said.

“We can image different stages of breast development, immune cells, lymph nodes and hair follicles and watch how individually-labelled cells function.”

“This means we can create beautiful images with extremely fine details about the cell shapes to get a better understanding of how cells interact and change over time. This opens up many new research opportunities and we are only just starting to see the potential of what this could be used for.”

Dr Dawson said he hoped the imaging protocol would make this type of imaging more widely accessible to researchers.

“There are very few research institutions doing this really high-end imaging, so it is great that we have this capacity in Melbourne and can share it with research teams worldwide.”

The original news article was posted on the WEHI website. Video courtesy of WEHI.

ACRF has awarded $10m in grants to WEHI for cancer research. Our esteemed Medical Research Advisory Committee ensures that only the most promising cancer research initiatives in Australia receive our funding. If you would like to financially contribute, please go to acrf.com.au/donate