#CureForCancer – Page 4 – Blog about neuroblastoma research

#AskLuiza: Could we use blood tests to detect neuroblastoma?

For most neuroblastoma cases a tissue biopsy, which means remove a piece of the tumour and analyse under a microscope, is performed to confirm the diagnosis, allow the risk stratification (low, intermediate or high-risk cancer) and determine treatment. However, it is not always possible to perform a biopsy. In these cases, other tests are available such as ultrasound, x-ray and urine test¹. Although these tests help the diagnostic, they are much less informative to determine the risk group and to guide treatment.

Cancer is a genetic disease and as such several genetic alterations are present in the DNA and can be useful to determine a diagnostic and prognostic of the disease. These alterations can also be useful to monitor treatment effects. But, how we can examine the DNA without using a piece of the tumour?

The answer for that relies on our blood. Cancer patients have cancer cells circulating in their blood and these cells release what we call cell-free tumour DNA. The level of cell-free tumour DNA in the blood of a healthy individual is low while this is increased in cancer patients. The detection of cell-free tumour DNA with specific alterations may help to not only detect the disease but also determine if the tumour cells are changing after treatment.

Recently, a trial for a blood test that can detect 50 different types of cancer was launched in the UK². The test called the Galleri test look for cell-free tumour DNA in the blood using modern genetic sequencing technology. It spots the DNA that has changes common in specific cancers but not seen in healthy cells.

One of the main questions of this trial is if the test can find early stages of cancers. Although neuroblastoma is cancer that could benefit from this test, unfortunately, it is not one of the cancer types detected. However, the presence of cell-free tumour DNA was already detected in neuroblastoma patients’ blood³. Moreover, several alterations in the DNA of neuroblastoma patients have already been reported to have predictive value for disease progression and treatment monitoring. These alterations include the increase in the number of specific genes, genes breakdown or increased activity of certain genes. Their presence may indicate poor outcomes and early detection could guide to specific treatment options.

The big challenge is to have a non-invasive diagnostic method, such as blood tests, that are sensitive enough to detect the early stages of the disease. Specifically for neuroblastoma, comprehensive analysis in clinical trials regarding cell-free DNA levels and their specific changes over time would help to advance the development of liquid biopsies, such as blood tests, for this type of tumour.

Written by Luiza Erthal

References

1. Tests for neuroblastoma, Cancer Research UK. February 25, 2021

2. The Galleri multi-cancer blood test: What you need to know, Harry Jenkins, Cancer Research UK. September 13, 2021.

3. Wei, M., Ye, M., Dong, K. & Dong, R. Circulating tumor DNA in neuroblastoma. Pediatr. Blood Cancer 67, (2020).

#AskLuiza about neuroblastoma biology

#AskLuiza

We are launching a new initiative #AskLuiza to help the public and patients know more about advances and current trends in neuroblastoma.

Luiza is a research writer at the Cancer Bioengineering Research Group. She holds a PhD in Biomedical Sciences from Trinity College Dublin. You will ask a question and Luiza will look for the answer in peer-reviewed research papers that the research community trust.

Leave your question and follow our blog to read the answer soon: https://forms.gle/vrgwKoZivyUVawk9A

Models to study neuroblastoma in the laboratory

Finding suitable research models to study disease is a big challenge for researchers around the world. In cancer research, it is essential to work with models that can recapitulate tumour characteristics as much as possible. This is important to test chemotherapeutic drugs, understand tumour behaviour and have higher chances of translating the finds from the laboratory to clinical practice.

Multiple factors influence tumour behaviour and disease progression. The most important is the tumour microenvironment, which comprises different cells and molecules that surround the tumour and the extracellular matrix, a network of molecules that provides support to the cells in the body.

Most cell studies in a laboratory are based on 2D cell culture models in which the cells grow in a monolayer. Although this approach has a low cost and it is easy to use, it lacks the complexity observed in the clinical scenario. It is true that no model can recapitulate all the complexity found in the body. However, scientists were able to develop interesting approaches to study different tumour characteristics with relatively good approximation¹.

Specifically for neuroblastoma, the most common solid tumour that affects children, scientists developed 3D models in which neuroblastoma cells grow interacting with the surrounding environment and with each other in a vial. Examples of 3D models include cells grown in hydrogels or scaffolds and multicellular tumour spheroids (see image below). Spheroids are formed through the self-adhesion of tumour cells growing in the form of very small balls. They can be maintained in the laboratory on their own or supported by scaffold-based platforms (jelly-like or porous materials). Scaffolds essentially support the cell resembling the extracellular matrix and surrounding tissue in the body.

*Credits for the image: 3D models to study neuroblastoma. Adapted from Nolan, J. C. et al. Preclinical models for neuroblastoma: Advances and challenges. Cancer Lett. 474, 53–62 (2020).*

In the Cancer Bioengineering Research Group, we work with neuroblastoma models such as organoids, a more complex type of spheroid, to understand neuroblastoma migration and invasion². Moreover, we recently shared with the research community a protocol at jove.com describing the development of a 3D neuroblastoma model using collagen-based scaffolds³.

Time-lapse video of neuroblastoma organoids’ growth. Accompanying experimental data published in Gavin et al., Cancers 2021. Source: the Cancer Bioengineering Research Group

These models have the potential to advance drug tests performed in the laboratory providing better clinical translation, ultimately contributing to improving the quality of life and survival of children diagnosed with neuroblastoma.

The work with 3D models at the Cancer Bioengineering Research Group is supported by the Irish Research Council, the Conor Foley Neuroblastoma Cancer Research Foundation, Neuroblastoma UK and National Children’s Research Centre.

Written by Luiza Erthal

References

1. Nolan, J. C. et al. Preclinical models for neuroblastoma: Advances and challenges. Cancer Lett. 474, 53–62 (2020).

2. Gavin, C. et al. Neuroblastoma Invasion Strategies Are Regulated by the Extracellular Matrix. Cancers 13, 736 (2021).

3. Gallagher, C., Murphy, C., O’Brien, F. J. & Piskareva, O. Three-dimensional In Vitro Biomimetic Model of Neuroblastoma using Collagen-based Scaffolds. J. Vis. Exp. 62627 (2021) doi:10.3791/62627.

A 30km Dublin Mountain Way in A Day

And the story began with a meeting of fantastic 7 at the very beginning of Dublin Mountains Way in Tallaght at 6.30 am on September 25th. The spirit, cheer, backpacks with essentials and branded tops were on, Strava was launched and we swiftly headed off.

It was quiet, dark and cheering. No one was on the streets, a few cars passed by. We took towards Bohernabreena reservoir through the sleepy estates of Tallaght, sensing the sunset. Clouds were low and the highest peaks in the Dublin Mountains including Seefingan, Corrig and the highest, Kippure were in the mist. Nevertheless, we were full of energy and hopes to see it later.

Cheat chats and jokes were here and there, we walked in small dynamic groups recalling our pre-covid life and stories that happened during the lockdown. A mix of newbies and maturating research students. We met some in person for the first time since the COVID restrictions admitting that our visual senses are extremely important to memorise a person and recognise him/her on the next occasion. We were enjoying this face-to-face communication and our team re-connection.

The first 8 km flew in a flash. We stopped for our breakfast in Dublin Mountains. The grass was wet, the sky was blue. Mountains started to draw their shape through the clouds. Yoghurts, fruits, bars immediately disappeared in our stomachs. Everyone was happy to lighten their backpack. Every little helps!

A few plasters were glued, and we continued on at a very good pace. The sky was changing with sunny spells. We travelled around Spinkeen and Killakee at their base doing up and downhills and verifying our route with the hiking app. At the 20 km mark, we stopped for lunch. Sandwiches, grapes, mandarines and sweets were shared and eaten and then polished with chocolates from the recent Nadiya’s home trip. Jellies left untouched.

At 25 km, our blisters reminded us of being humans. Our pace slowed down and we started a very mild ascent to Tibradden Mountain leaving the Pine Forest or Tibradden Wood behind. We climbed further to Fairy Castle, the highest point on the Dublin Mountains Way (537m). Throughout the entire way, Dublin showed its best views of the Phoenix Park and the Pope Cross, house roofs, Aviva Stadium, two Chimneys, Dublin Port… The scenery was fascinating and breathtaking. We saw Howth and Dun Laoghaire, Sugar Loaf… We met groups of Germans, French, Irish and many others.

At Three Rocks Mountain/Fairy Castle, we started our descent and entered Tiknock forest. This part was steep. We crossed the Gap Mountain Bike Adventure Park to reach Glencullen. Got lost at the end but just for a sec and reached the Glencullen junction at 2.30pm. It took us 8 hours with walks and stops from start to finish to complete the 30 km challenge in a day. We got tired but felt happy and satisfied.

We aimed to raise awareness of childhood cancer in general and neuroblastoma in particular as well as honour children with cancer, their parents, siblings, friends and careers, doctors and nurses, volunteers in the hospitals and researchers working to find cancer weaknesses and develop new treatments that are friendly to patients and target cancer aggressiveness.

We will count our tally in the coming days and transfer it to three wonderful charities that support childhood cancer research.

We thank everyone who supported this challenge!

Go raibh maith agat!

I’m Ronja

I’m Ronja, I’m from Germany, but have spent my entire adult life in the English-speaking parts of this world. Right after school, I interned with a PhD student working on cystic fibrosis for a couple of months. Having the chance to culture airway epithelial cells myself made me certain I was on the right track with biomedical sciences. So, I studied Biomedical Sciences (Anatomy) in Aberdeen. The best part of that degree was my introduction to dissections. I enjoyed them so much that I even considered becoming a full-time prosector. But that does not count as essential work, so I found a remote master’s degree in Health Research instead. Studying remotely gave me the fabulous opportunity to structure my own time. I could go and explore Scotland during the day and work in the evenings. But after 5 years of studying, I was finally ready to start a PhD and was ever so delighted when I heard I could weave in some dissections at RCSI. Now, I’m looking forward to discovering what Dublin has to offer and to getting stuck in my research project!

While I didn’t know much about the particulars of my PhD before starting, I had an idea about the project from the application and I knew accommodation was sorted out for me, but I had never seen the place or my future flatmates. The one thing that I was made aware of far in advance of moving to Dublin was that September was Child Cancer Awareness Month, for which the team was going to do a charity event. Based on past years I was expecting it to be a 10km run, which was pretty daunting to me. So, I prepared. I started running and cycling over the summer until 10km weren’t an issue anymore. But in the first lab meeting plans shifted. We were going to do the Dublin Mountains Way in a day. The 10km were tripled and depending on donations maybe even quadrupled. Quite a different challenge! But I believe my summer prepared me well for that too. Alongside running I started cycling a little as well. And because there was a free bike in Aberdeen for me, I cycled it down to Stirling. Let’s hope that the endurance needed to cycle 200km translate to hiking 30-42km!

Dublin Mountain Way in A Day, September 25th 2021

Here are our plans. This year we have upped the challenge, taking on the Dublin Mountain’s Way in a Day ⛰ We will hike through the Dublin Mountains from Tallaght to Glencullen, and maybe even all the way to Shankill on September 25th! Our challenge is not only to do #DMW in a Day & support three wonderful charities CMRF Crumlin/National Children’s Research Centre, Neuroblastoma UK and the Conor Foley Neuroblastoma Cancer Research Foundation but also beat our past fundraising records! If we raise 2K+, we’ll do 30km in a day. If 3K+ then 42km! Can u challenge us? All funds raised will go to the 3 selected charities. Every donation big or small is hugely appreciated!

Please support us by donating to our Gofundme

Childhood Cancer Awareness Month 2021

Every 100th cancer patient is a child. Cancer is the 2nd most common cause of death among children after accidents.

Childhood cancer is an umbrella term for many other types of this disease. Every September, many charities, researchers and parents of children with cancer work hard to raise awareness of this cancer. You may learn more about kids with cancer, their loving families, the doctors and caregivers who looking after them and treating them, the young survivors of cancer and those kids and teens who lost their battle, and the scientists who working hard to find a way to stop childhood cancer.

This year our research team will hike Dublin Mountain Way in One Day on the 25th of September 2021 whatever the weather in honour of Childhood Cancer Awareness Month. For every one euro donated to research only 1 cent of this goes to ALL childhood health conditions including cancer. Therefore, the donations we receive will be split equally among some wonderful children’s charities. These charities include the Conor Foley Neuroblastoma Research Foundation (CFNRF), Neuroblastoma UK (NBUK), Children’s Research & Medical Foundation (CRMF) Crumlin.

If you would like to get involved in this amazing challenge and help us raise vital funds for childhood cancers, you can contribute to our fundraising page:

A warm welcome to our new PhD students!

A warm welcome to our new PhD students Ronja and Erin! Both received the prestigious Irish Research Council – Enterprise Partnership Scheme Award. Indeed, I am a proud PI. This competitive scheme brings the most promising researchers to advance our knowledge across many disciplines, e.g. Law, Astronomy, Sociology, Biomedical Sciences and many more. A key element of this scheme is to work together with an Enterprise Partner.

We will work closely with the Conor Foley Neuroblastoma Cancer Research Foundation – a research charity led by the family who lost their child to neuroblastoma. An inspirational example of never giving up.

We will continue to dissect neuroblastoma biology using innovative platforms such as tumour-on-chip and 3D scaffold-based models in collaboration with our colleagues in the Tissue Engineering Research Group at RCSI and the Fraunhofer Project Centre at DCU.

This announcement is timely to celebrate Childhood Cancer Awareness Month in September.

Two talented and dedicated young scientists are joining our team. In 4 years time, we will have another pic of their graduation on the same stairs.

Upwards and onwards!!

International Childhood Cancer Awareness Day 2021

Every year, we celebrate Childhood Cancer Awareness Day Internationally. Pre-COVID times, it was straightforward to do a coffee morning, a bake sale, or as we did a Hot Chocholate morning.

To be honest with you, I had almost no presence of childhood cancer in my life until I joined Prof Stallings lab in 2011. When I said ‘almost’, I meant during my adulthood.

My Dad had a younger brother, both started their families at the same time. Our families used to spend a good time together, holidays, birthdays and weekends together. Both I and my cousin Igor were born almost within a year. I remember our play days together but at the level of feelings and stories told by my parents. In the pic, we were held by my nanna.

I do not have a pic where we were 3- or 4-years old. No pic was taken after Igor was diagnosed with blood cancer. He was 1-1.5-year-old. He travelled 800km to the best paediatric oncologists to receive the most progressive treatment back then. It extended his time with the family by four years. But he lost his battle…

How much can remember a 1-, 2-, 4- years old? My last memory – Igor was sleeping in a neat coffin. Adults were muttering. I remember, a tear slowly rolled down from Igor’s closed eyes. I naively asked my nanny why did the dead cousin cry??? He did not want to leave us, – said my nanny softly.

Back then parents were not much informed on the disease, treatments, odds and alternative options. Igor was suffering, no pain relief options were available… No palliative care… Remember my nanny’s words: “These doctors had no hearts. All this child needed was a sense of peace, quiet time with his parents away from the hospital wards”.

Many things have changed since then. Eight out of 10 children with blood cancer are responding to treatment well, they reach adulthood, may even have kids of their own. However, there are some types of childhood cancers that do not respond well and can return to being more aggressive. Cancer steals the child’s future. One of the thieves is neuroblastoma, a solid tumour of undeveloped nerves.

Childhood cancer research is essential to return happy days to kids and their families. Many childhood cancer research charities do their best to secure funds and support researchers like me. It is vital to have a continuous investment in research that helps to understand the weakness of childhood cancer and develop new drugs designed exclusively for kids.

Today I want to thank 3 charities for their hard work: Children’s Health Foundation Crumlin, Neuroblastoma UK and the Conor Foley Neuroblastoma Cancer Research Foundation. And ask you, my readers, to donate to a childhood cancer charity of your choice.

How neuroblastoma cells spread?

Since I joined neuroblastoma research, I have been puzzled by the fact that half of the children with neuroblastoma have the disease spread at the time of diagnosis. It is still a puzzle whether cells spread and primary tumour growth happen simultaneously or more adventurous cancer cells escape the primary tumour location later.

At a cancer conference, I met Prof Ewald who studies this process in breast cancer. I was fascinated by the approach and started to look for opportunities to join his lab. To tell the truth, very few exist for mid-stage career scientists! One of them is the Fulbright program.

One day, I opened my email saying that I received a Fulbright-HRB Health Impact Scholar Award to travel to Johns Hopkins University and adapt their 3D models to learn how neuroblastoma spreads. It was a life-changing experience both personally and professionally. The amount of experimental data collected over 4 months of work did not fit a 1TB memory stick! Indeed, this short journey was just a start of a new research inquiry.

On my return home, the greatest task that remained was to make sense of every single experiment. Cian Gavin took over and spent almost a year systematising, characterising it, and placing it into a context. It was meticulous work with very little known about invasion strategies in neuroblastoma. Now, we are happy to share our findings published on Cancers.

Where do we go now? Well, our next step is to understand the cellular players behind neuroblastoma invasion and how we can target them to stop neuroblastoma spread. It won’t be a short and sweet journey, but we are ready for it!

This fantastic and rewarding work was supported by Fulbright Commission Ireland, National Children’s Research Centre, Health Research Board, Science Foundation Ireland, the National Institutes of Health/National Cancer Institute (Prof Ewald), Alex’s Lemonade Stand Foundation for the COG Childhood Cancer Repository (Prof Reynolds) and the National Institutes of Health/National Cancer Institute (Prof Reynolds).