Research

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Professor Ursula Kees’ Farewell Letter

Dear Foundation Supporter,

I have dedicated 34 years of my life to studying infant cancer at the Children’s Leukaemia & Cancer Research Laboratory.

With a grateful heart, I say thank you to the Foundation and its supporters for bringing me from Switzerland to Perth and giving me the chance to lead the Laboratory. It is with some sadness, that I announce that I have come to the end of my time as one of the founding scientists of the Children’s Leukaemia & Cancer Research Foundation (Inc.) (CLCRF) Laboratory.

During these 34 years, I have been struck by one word to describe the effects of infant cancer: AGGRESSIVE. Cancer in children is not the same as adult cancer. An adult cancer patient will experience five to 30 years of life lost due to cancer and its treatment. A child who is under 12 months of age is likely to lose 67 years of life through cancer and its treatments.

Sadly, one in 500 Australian children will develop cancer before age 15. Childhood cancer is still the leading cause of death from disease for Australian children.

Our Laboratory team has contributed to a world-wide effort to find better therapies for our young cancer patients – with great outcomes. In the mid-eighties, many patients did not survive. Today, successful therapies are available for the majority of our young cancer patients.

Here is a big BUT. Some of our patients initially respond to the therapy they are given, but soon the disease is back. This is devastating for the patient, the parents and siblings, for the doctors and nurses and for the researchers. My desire to help children survive through this terrible disease has driven me and my team these 34 years. We search for answers to fight childhood cancer in the Laboratory to bring better therapies to the patient.

For each patient, a treatment plan is worked out. The length of therapy may be a few months or up to three years. A patient may receive one form of treatment or a combination, depending on what researchers have found to be the most effective in destroying the patient’s particular type of cancer cells.

The most common types of treatment are chemotherapy, radiotherapy and surgery. I started in the CLCRF Laboratory in 1984, at a time when a new treatment was talked about, called ‘bone marrow transplantation’. Dr Michael Willoughby, the specialist who diagnosed and treated childhood cancer patients at the children’s hospital, was a pioneer of this treatment. In what turned out to be a great collaboration, our Laboratory team was able to contribute to the Bone Marrow Transplantation Program at Princess Margaret Hospital. Many lives have been saved through this Program.

Some patients receive chemotherapy over three years – a very long time. For the first few weeks they are in hospital and afterwards they have to come to the children’s hospital for treatment – many times over three years.

They are given up to 12 different drugs that destroy the cancer cells. However, these very potent drugs can also cause damage to the patient’s healthy cells. These effects are short-term and long-term, because they cause harm to the growing bodies of the young patients.

Long-term effects of the treatment can be heart damage, second cancers, lung damage, infertility, cognitive issues, hearing losses and much more. Two-thirds of those who survive must face at least one chronic health condition for the rest of their lives. So, our key goal in the CLCRF Laboratory is to find therapies that have none of these long-term effects.

Leukaemia is a cancer of the blood. The leukaemia cells multiply uncontrollably, such that they crowd out the healthy blood cells. Leukaemia is the most common cancer in children. In a world-wide research effort, we helped to develop treatment protocols for leukaemia patients. They are very successful – today more than 85% of patients survive.

Sadly, this is not the case for babies who are diagnosed with leukaemia. Less than 40% survive. Our Laboratory team has focused on these very young patients, to find out why they do not respond to the drugs as well as older children do. What is the difference?

We found that the ‘mistakes’ or mutations that turn a healthy blood cell into a baby’s leukaemia cells are different from those in older children.

We managed to grow leukaemia cells from babies in the Laboratory, which was only possible because Jette Ford from our team has the skills to keep the leukaemia cells alive, such that they multiply – and we have a cell line.

Without these unique cell lines, our research to find better therapies could not have happened. The cell lines are absolutely critical to make a change for our youngest leukaemia patients. We screened many drugs that have come to market, and we found some that can destroy the leukaemia cells from the babies. Not only that, we also found out that these drugs work very well in combination. Best of all, these new drug combinations have fewer side effects.

It’s a matter of life and death.

By giving to the CLCRF you can help to improve the survival rate of children with cancer and better their response to treatment.

I am proud to say that our CLCRF Laboratory has attracted worldwide attention with our research into infant cancer. In Perth, our Laboratory boasts cell lines for testing that have been used across the world so that we can develop the best drug combinations to treat childhood cancer.

The CLCRF Laboratory is not government funded. Only one per cent of government funding is given to children’s cancer research. That is why your help is vital in the search for better treatment for children with cancer.

We rely on you to continue the dream of improving the lives of children with cancer. You can do this by investing in the legacy of research that we started.

 There are still many drug combinations that our laboratory aims to test to better the lives of children with cancer. This testing is vital so that we can see more children survive, but we cannot do this without your help. Your money goes towards increasing their chances of survival and enhancing their lives.

In order for the Laboratory to continue with this life-changing research, we need your help. So please dig deep and give generously to the CLCRF.

To demonstrate my belief in this key research that the CLCRF Laboratory is leading, I will continue to be a board member of the CLCRF.

You’ve been so generous in the past, we are very thankful. The wonderful team of researchers that I have lead for 34 years is working around the clock to find the answers to make children’s lives better. But time is running out, so make a donation now to the Children’s Leukaemia & Cancer Research Foundation (Inc.) to help these little ones who suffer so greatly.

Yours sincerely,

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 Professor Ursula Kees

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Dr Stirnweiss Makes Inroads into Fighting Resistant Cancer

Last year Dr Anja Stirnweiss, Senior Researcher at the Telethon Kids Institute, received a Children’s Leukaemia & Cancer Research Foundation (Inc.) (CLCRF) Project Grant that enabled her to evaluate pathways associated with drug resistance in NUT midline carcinoma, a type of aggressive cancer.

Further to this experimental work being conducted and analysed, Dr Stirnweiss submitted a Small Grant Application to CLCRF for support with the costs to finalise and publish the findings of this project.

In NUT midline carcinoma, the patient’s genetic material is incorrectly repaired, which leads to the joining of two genes (called BRD4 and NUT) and creates a new hybrid gene that causes the cancer. A new class of cancer drugs called iBETs, designed to block the function of BRD4, are currently assessed worldwide in 21 clinical trials for patients with leukaemia, brain tumours, aggressive breast cancers and NUT midline carcinoma.

Dr Stirnweiss’ findings indicate that the therapeutic benefits of these drugs are limited through the acquisition of resistance. This has important clinical ramifications.

For the study, she and her team used a unique collection of cell lines, obtained from NUT midline carcinoma patients, to identify drug-induced changes in gene expression. Dr Stirnweiss then performed a correlation analysis to identify changes that are unique to iBET-resistant cells.

Network analysis, which assesses how those genes are functionally connected to each other, highlighted the oncogene FOS to be a central player of the gene network that is associated with drug resistance. Removal of this gene from the resistant cells showed that FOS is not a driver of resistance, but an ideal marker to predict whether the cancer cells will respond to iBET drug treatment. Ultimately, assessment of FOS could be used in the clinic to predict whether patients will benefit from iBET treatment.

It was agreed that the findings from this substantial body of work is highly relevant to patients with NUT midline carcinoma and other cancers with BRD4 involvement. Therefore, the findings should be made available to other researchers and clinicians. To publish these findings in the highly prestigious journal, Molecular Cancer Research, minor work needs to be done. When completed, Ms Mahalia McEvoy, an outstanding young researcher who conducted experiments essential to the proposed manuscript as part of her Honours studies, will assist Dr Stirnweiss with writing the manuscript.

The Foundation approved a budget of $14,276 to cover these publication costs. Dr Stirnweiss passionately believes that this research presents a unique opportunity to make a difference for patients suffering from NUT midline carcinoma.

Congratulations and thank you to Dr Stirnweiss for her outstanding scientific contribution to cancer research.

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Cracking the Cancer Code for Kids

‘Excitement’ and ‘cancer’ are two words that shouldn’t really go together, until you add the word ‘hope’ to the sentence. Those are the words flowing out of the mouths of researchers from the Telethon Kids Institute in Perth as they edge closer to answering what causes pediatric cancer, thanks to funding by the Children’s Leukaemia & Cancer Research Foundation (Inc.).

Dr Mark Cruickshank, who leads the Cancer Genomics and Epigenetics team, said it has been a long road to reach the pointy end of years of research and is excited to be on the verge of cracking the cancer code for kids. “This is one project where we have no idea what causes leukaemia in infants and that’s a really big focus of mine at present, because I’m very close to finding what we think are the answers to that conundrum,” Dr Cruickshank said. “It has taken more than four years to reach this stage, by studying the gene sequencing mutations in cells. This in turn has now escalated the drug therapy studies that are built on that gene research.”

Dr Cruickshank revealed that the research team has been analysing data from cancer cells of infants to identify mutations that are not present in patients’ healthy cells. As infants are ‘brand new’ to life they have had little time for their cells to mutate outside the womb, so there is something genetic causing them to have cancer. “We’ve found some extremely exciting signals from the data, statistical signals, and now we need to test these out in the laboratory. This could be a huge advancement and it could open up a lot of different avenues, for example we could look at cohorts of patients to see if a mutation is associated with treatment outcomes,” he said.

The genetic research and understanding has been crucial to take the team to this next stage as the make-up of the leukaemia affects whether the treatments will work or not. Having a genetic understanding can cut out the guessing games so patients can receive doses of drugs that are effective and also minimise the side effects to their bodies. “We already know some drugs fail in some patients and we think this is due to the genetics,” Dr Cruickshank said.

 While researchers may have found the causes of the diseases, the next step is to develop the best treatment protocols to deliver to patients and their families.

“I don’t really think that gaining short amounts of extensions of life is where we need to end up, we really need to cure these diseases. I want to reach a point where the therapies aren’t putting the families through a year’s worth of pain and then a lifetime of uncertainty,” he said.

“I believe in finding absolute cures – and that is the goal of the research, to do that we need help. To accelerate the research we need to be able to test the drugs in all different ways and we need the best technologies. We have the capacity to do this, but it takes money to do it.”

If you would like to contribute support to Dr Cruickshank and his team’s research to help make a difference you can donate to CLCRF or contact the Foundation via email or phone +61 8 9363 7400 for further information.

Read a recent paper on infant leukaemia cell lines and drug screening published in Volume 31 of Leukemia Journal by Dr Mark Cruickshank

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CLCRF funding to Dr A. Beesley

A landmark study that lifts the lid on key features of one of the most hostile cancers will soon be published with funding from the CLCRF.

One of the Foundation’s Fellowship recipients, Dr Alex Beesley with Dr Anja Stirnweiss have comprehensively described, for the first time, the genetics behind NUT Carcinoma.

NUT Carcinoma is one of the most aggressive human cancers, and there is a desperate need for effective therapies for patients with this illness. It is a rare genetically defined disease not specific to any tissue type or organ and common sites include the head and neck.

So far the cancer has been very resistant to standard chemotherapy treatments. Specialists have found that tumours may initially respond to therapy, but then rapid recurrence is experienced. Treatment must be tailored to the individual patient.

The study is a culmination of the research program that the Foundation has funded over the last several years, both in the form of project grants and Dr Beesley’s CLCRF Fellowship. This latest award of $12,000 will assist in the publication of the highly important document.

It is hoped that the manuscript will be submitted to the journal Oncotarget and it represents a milestone publication that will help inform therapy choices for this aggressive cancer.

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Charity Golf Day Royal Perth Golf Club

They may be more accustomed to green turf and and getting out of sand traps, but representatives from Royal Perth Golf Club embraced the chance to step into scientific surrounds on a visit to the CLCRF Research Lab.

Under the wing of tour guide Professor Ursula Kees, the golfers learned about very different challenges the researchers came up against each day as they strive to find answers to how they can help children with cancer.

It was an eye opening visit to see just what is taking place in the lab funded by CLCRF. They witnessed where and how the ‘cell lines’ taken from tumours of infants who are fighting or have survived cancer are being used to develop more effective treatment protocols for children around the world.

It was an ‘ace’ shot for the Foundation to make a great impression on the captivated audience. CLCRF has now been chosen as the 2017 beneficiary of the Royal Perth Golf Club’s annual charity day.

Thank you to the Royal Perth Golf Club for their generous support. Further details about the day will follow.

Child Cancer Leukaemia Treatment – Research Sheds New Light

A Telethon Kids Institute Research study examining drug resistance in leukaemia patients has shed new light on why some treatments may be more effective than others.

The study, which looked at cells from children suffering from T-cell acute lymphoblastic leukaemia (T-ALL), examined how different genes were associated with resistance to different drugs in an effort to improve treatment success.

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