#CureForCancer – Blog about neuroblastoma research

#JournalClub with Shreya: Modelling Brain Tumour Spread

This article by Krieger et al. discusses the most common form of brain cancer called glioblastoma. Due to its highly aggressive nature, research must be conducted consistently and rapidly to develop new treatments. This has proven challenging due to primary tumours being resected before further research can be done, as well as the lack of current technologies to fully explore relationships between GBM and surrounding brain tissues. This study aimed to study the aforementioned interactions in under 4 weeks, accounting for the rapid progression of the disease in real life.

GBM cells were first derived from four patients and treated with glutamine, heparin, epidermal and fibroblast growth factors, then underwent a sequence of manipulations, such as second-generation replication lentivirus infection of GBM cells, iPSC line 409b2 inoculation in Aggrewell plates and later manipulation with invasion assays, and scRNA sequencing, which, along with the Aggrewell cells, produced neural progenitor cell spheroids for analysis. Confocal microscopy and the developed image processing algorithm allowed for visualization of these cells following fluoroscopy and depicted consistent growth of tumour cells. There was also the growth of microtubules. Any dissociated organoids were then co-cultured with GBM cells again, promoting interaction between the two. Further analysis revealed the upregulation of 45 genes, including PAX6, GJA1, GPC3, and others involved in cell regulation.

Credit to Teresa G Krieger, Stephan M Tirier, Jeongbin Park, Katharina Jechow, Tanja Eisemann, Heike Peterziel, Peter Angel, Roland Eils, Christian Conrad, Modeling glioblastoma invasion using human brain organoids and single-cell transcriptomics, Neuro-Oncology, Volume 22, Issue 8, August 2020, Pages 1138–1149

In conclusion, this novel mechanism of analysis of GBM cells using Aggrewell plates provided fruitful results, indicating intricate relationships between GBM cells and organoids, providing crucial insight for treatments by elucidating specific gene expression, heterogeneity of cells, and offering new targets based on ligand-receptor interactions. The particular relevance of this study to my work is regarding the usage of Aggrewell plates, which I am currently studying to determine how best to keep cells growing successfully within the wells. This article proves the usability and efficiency of Aggrewell and establishes its crucial role in the realm of brain cancer treatment research.

Written by Shreya Sankar

#JournalClub: Anti-Cancer Immunotherapy

Hi there, Federica here! In the fast-paced world of scientific research, staying informed about the latest studies and breakthroughs is crucial. It enables researchers to build upon existing knowledge, avoid redundant efforts, and discover new directions for their work. That’s why we’ve started a new series of blog posts highlighting recent papers and explaining their significance for our research.

Recently, a fascinating study explored an innovative method to boost the effectiveness of cancer immunotherapy: “A combination of a TLR7/8 agonist and an epigenetic inhibitor suppresses triple-negative breast cancer through triggering anti-tumour immune“.

The researchers investigated a combination of immune checkpoint blockade (ICB) and other drugs to turn “immune-cold” tumours (which evade the immune system) into “immune-hot” tumours (which the immune system can attack). They developed a special delivery system using nanoparticles called metal-organic frameworks (MOFs). These nanoparticles were loaded with two types of drugs—a TLR7/8 agonist and an epigenetic inhibitor (BRD4 inhibitor). To make the nanoparticles even more effective, they were coated with vesicles from the cancer cells themselves. This coating helps the nanoparticles specifically target cancer cells.

But how does it work?

The nanoparticles are designed to find and enter triple-negative breast cancer (TNBC) cells. Once inside, the drugs prompt the cancer cells to break apart and release signals that alert the immune system. These signals attract dendritic cells, which then activate CD8+ T cells—the body’s natural cancer fighters. The TLR7/8 agonist further enhances this immune response, making the treatment more powerful.

In both laboratory tests and animal models, this method showed significant promise. It not only slowed down tumour growth but also improved the body’s immune response to cancer. Importantly, the study found that this approach could remodel the tumour environment, making it more hostile to cancer cells. For example, they wanted to verify that their combined delivery system could really boost the body’s ability to fight tumours. They focused on a protein called calreticulin (CRT) that, when it shows up on the surface of tumour cells, helps the immune system spot and remove them. They found that when they used their special delivery system (CM@UN and MCM@UN), the levels of CRT on the surface of tumour cells went way up. This was especially true for the MCM@UN group, showing just how powerful their method was in getting the immune system to attack the tumours.

*The original image was published in J Nanobiotechnology. 2024; 22: 296.*

So, why is this study important for my work?

The principles of enhancing the immune system’s ability to fight cancer are central to both the research in the study and in my project. Like the nanoparticles in the study, mRNA vaccines can be designed to specifically target cancer cells, ensuring that the treatment reaches its intended destination. Another similarity is how the drugs activate the immune system, which parallels how mRNA vaccines work—by training the immune system to recognise and attack cancer cells.

I find this study really interesting as it sheds light on innovative strategies for cancer treatment and provides valuable insights that can inform and inspire our research on developing mRNA vaccines for childhood neuroblastoma!

Written by Federica Cottone

International Childhood Cancer Day – 15 February 2024

We are celebrating #ICCD2024 with a Bake Sale and a Quiz. To earn a piece of cake, you have to answer a question correctly! Have a look at some:

Which civilisation first described cancer?
Where did the word cancer come from?
Do children get cancer?
What is the most common type of cancer in children?
Can the Human Papillomavirus (HPV) vaccine prevent cancer?
Can neuroblastoma begin to develop before birth?
What is the name of the nerve cell in which neuroblastoma begins to grow?
Can a child have a genetic predisposition to neuroblastoma?
What % stands for the incidence of neuroblastoma: 8 or 15?
What % stands for the neuroblastoma-related deaths: 8 or 15?
Does neuroblastoma first appear in the brain?
What does the letter N stand for in the gene MYCN?
How often does childhood cancer occur compared to adults?
How often does hereditary cancer happen in general?
Do you think that children are small adults when we talk about anticancer treatment?

Knit-A-Thon 2023 Results

A wonderful day of knitting – Knit-A-Thon-2023 raised 913 euros. A massive thank you to everyone who stopped by and donated on the day and beyond. Every cent counts! The money was split evenly between our four chosen charities: The Conor Foley Neuroblastoma Research Foundation (CFNRF), Neuroblastoma UK (NBUK), Oscars Kids and Childhood Cancer Ireland (CCI). These charities were established and are run by parents, some of whom lost their children to cancer. They continue their children’s legacy, doing an amazing job of advocating for children with cancer and better funding for research and aftercare.

And a special thank you to Ciara’s mam Aggie for the amazing handmade raffle prizes (chromosomes, antibodies, cup holders and many more) and a Master class on the day! We thank Jenny Duffy (RCSI Events and Communications Coordinator) for her time crocheting with us and for us! Thanks to Anggie’s and Jenny’s skills, there were lots of mascots to win – and many of them collected already. We much appreciate the support from the RCSI Estates and Porters who looked after us on the day.

Go Raibh Maith Agat!!!

MANY THANKS FOR YOUR BIG HEARTS!!!

Knit-A-Thon 2023

We are the Cancer Bioengineering Group, and September is a very special month for us as it is Childhood Cancer Awareness Month. Childhood cancer is the 2^ndleading cause of death in children after accidents. Our group researches childhood cancer neuroblastoma, a cancer of immature nerve cells. Despite intensive multimodal treatment, as many as 1 in 5 children with aggressive neuroblastoma do not respond, and up to 50% of children that do respond experience disease recurrence with many metastatic tumours resistant to many drugs and more aggressive tumour behaviour that all too frequently results in death.

This is what we want to change! We believe that every child deserves a future, and our team of postgraduate researchers led by Dr Olga Piskareva is dedicated to strengthening our knowledge of this disease and identifying new potential ways to tackle it, as well as taking part in fundraising activities so our group and others can continue with this research.

On Tuesday, the 19^th of September, we are running a Knit-A-Thon using gold and purple yarn to mark childhood cancer and neuroblastoma, respectively. Our patterns are inspired by Neuroblastoma UK and Mr Google, indeed.

This year, we honour 4 charities that are doing an amazing job of advocating for children with cancer and better funding for research and aftercare. Therefore, the donations we receive will be split equally among The Conor Foley Neuroblastoma Research Foundation (CFNRF), Neuroblastoma UK (NBUK), Oscars Kids and Childhood Cancer Ireland (CCI). If you would like to get involved in the Knit-A-Thon and help us raise vital funds for childhood cancers, come along on the day and make a donation to these wonderful charities.

On the day, RCSI 123 SSG will #GoGold in support of this cause. Please come by to see the RCSI building lit up and share your pictures on social media with the hashtag #ChildhoodCancerAwarenessMonth to raise awareness.

Ready, Steady, Go!

Every year we manage to raise an amazing 1500-2000 euros by organising a new challenge. We are eager to surpass that target this year. All donations no matter how small are appreciated at GoFundMe.

Growing cancer cells in 3D

Hi there, Ciara here again, a final-year PhD student in our research group. I can’t believe September has rolled around again, meaning one thing: it’s Childhood Cancer Awareness Month (CCAM). In honour of this month, I would like to tell you a little bit about the childhood cancer we study in our lab and the research that I do to one day help save children from this disease.

Neuroblastoma is an aggressive childhood cancer, with sadly only 20% of late-stage patients surviving after 5 years. Progressive disease and cancer relapse are common in neuroblastoma. This is due to standard treatment regimens not being adequate for treating high-risk patients. Current treatment also may cause a series of adverse reactions in patients. Therefore, my research focuses on developing a 3D model of high-risk neuroblastoma that models the cancer more accurately in a laboratory setting. This will act as a beneficial platform to test whether new therapies effectively fight the patients’ cancer cells, leading to better treatment options for children with neuroblastoma.

Below is a picture of how we grow these cancerous cells on our 3D model and visualise them with fluorescent stains. When we can see them like this under a microscope, we can study how they move and grow to help us understand how to treat them.

Here, we can see the cells growing on our 3D cancer model. This image is magnified by 200 times to be able to see the individual cancer cells. The green stain is the outside of our cancer cells, or we use the term, the cell membrane. The blue is the inside, or as some of you may know the term, the nucleus of the cell. (It is amazing what we can see with the power of microscopes, right?)

As you may know, every year, we support amazing charities by raising vital funds to keep the fight against childhood cancer going. Keep your eyes peeled on our Twitter for updates on what crazy activity we have committed to this year!!

Written by Ciara Gallagher

Childhood Cancer Awareness Month 2023

Every September, we celebrate Childhood Cancer Awareness Month. This is a great opportunity to raise awareness about childhood cancer. Unfortunately, kids get cancer, too. While much research has been done to understand how cancer develops in adults, we still know very little about what exactly leads to cancer in children.

We are the Cancer BioEngineering Group led by Dr Olga Piskareva at the RCSI University of Medicine and Health Sciences. Our research focuses on neuroblastoma, an aggressive childhood cancer of immature nerves. The group has 7 PhD students developing research projects around neuroblastoma biology. One postgraduate student successfully defended her work and was awarded a PhD last month.

We are a dynamic group proud to be engaged in research, science communication and patient involvement. We do that through different initiatives. Throughout September, we will share many of them and invite you to keep following us on social media.

Our projects address topics related to neuroblastoma microenvironment, cell interactions, tumour resistance and the development of new therapies. To do that, we use 3D in vitro models, identify immunotherapeutic targets and evaluate extracellular vesicles.

We are always happy to answer questions and interact with the public. Follow us on our social media channels and read our blog to learn more about us and our research.

We are running a fundraising event, “A knit-a-thon,” on the 19^th of September. Stay tuned!

Thanks for reading, and we go ahead with neuroblastoma research!

Will there ever be one cure for cancer?

TL;DR – probably not.

Cancer is a disease which will have an impact on most people throughout their lifetimes, and there are few things that can bring people to agreement more than wanting a cure for this disease. But despite countless years of financial investments and researchers who dedicate their careers to cancer, we still don’t have a “cure”, and it can be difficult for non-scientists to fathom why.

One key concept to understand here is that cancer is not a single disease, does not have a single cause, and therefore cannot have a single cure. The differences between neuroblastoma and breast cancer are vast. And similarly, between patients with the same cancer type (e.g. two patients with breast cancer), the differences can be equally as big. Let’s for a minute, take an analogy of a large business company. (Disclaimer, I have never studied business in my life, so please humour me). The company is run by a CEO and board of directors and has many different departments with managers and teams of workers with specific roles. Suddenly, business is declining, and the company is not sure why. For one business, maybe this is down to someone in the Communications team spreading misinformation. For another, maybe a mistake has been made in the Finance team, which has had a knock-on effect on the other departments. Maybe Human Resources have not been properly reprimanding staff who have broken protocol. With hundreds of staff working in the company, it can be hard to pinpoint exactly where the problem has arisen, which has negatively impacted the company as a whole.

*Standard business hierarchy, created with BioRender.co*m

Human cells aren’t so different to a company. They have a central “nucleus” tasked with controlling the functioning of the cell as a whole (Board of Directors/Management). They have proteins which relay messages inside the cell, as well as outside with other surrounding cells (Communications). They have proteins which are responsible for detecting when something goes wrong, to correct or destroy whatever is acting out of place (Human Resources). Issues within any of the “departments” in a human cell can potentially lead to cancer, and just like our business model, it can be hard to trace where the problem arose, and it is often different between two cancers.

*Cell signalling networks, or the “business departments” within a cell, from* *Reactome.org*

For decades cancer was treated with chemotherapy, famous for attacking the good healthy cells as well as the bad. The research focus has now shifted towards more targeted therapies. An example of this is Herceptin therapy for breast cancer. This therapy targets a specific protein called HER2. HER2 is a team within the Communications department in breast cells. It receives communications from outside the cell, which tells the cell it’s time to grow, and relays this message to the Nucleus, which instructs proteins involved in cell growth to start this process. However, in some breast cancers, there are too many members in the HER2 team, all relaying this message to the Nucleus, resulting in too much cell growth. Herceptin is a drug which specifically targets HER2 and prevents it from relaying this message, effectively preventing the cancer cells from growing. While this can be very efficient at preventing tumour growth in HER2+ breast cancer, HER2 is not the culprit in all breast cancers. It is estimated that only 1 in 5 breast cancers have too many members in the HER2 team (Irish Cancer Society), and so targeting this will be inefficient in treating 4 out of 5 breast cancers. Meanwhile, cells of other cancers, such as liver or thyroid cancer, may not even have a HER2 team.

*BioRender (2020). HER2+ Breast Cancer*.

Hopefully, it is becoming clear why one “cure” will likely never be a reality. All cancers are different, all have different causes, and different employees breaking protocol. So, a one-size-fits-all approach simply can’t work. Instead, we need to focus on finding common company malpractices for each cancer, such as HER2 in breast cancer, generate a repertoire of different targeted treatment options depending on the various causes of cancer, and treat each patient as an individual investigation to determine what employee/protein is acting out of line to cause their cancer, so we can specifically reprimand them.

Written by Catherine Murphy

Paris…Paris…

I’m Ellen, and I am a 3rd year PhD student in the Cancer Bioengineering Group. Last week I attended and presented at my first international conference, ISCT (International Society for Cell & Gene Therapy), in Paris. I spent five days in Paris with three of them at the conference where scientists, researchers and pharma professionals came from far and wide. There was a strong focus on collaboration between industry teams and academics, and it gave me a lot to think about when it comes to my own PhD and career journey as a whole.

As a soon-to-be final-year student, the next step in my career has been on my mind. Starting out, I was very sure I wanted to progress within academia and follow the “traditional” researcher route. Industry always seemed so far removed from the basic sciences, and specifically biology research roles are hard to come by in Ireland. Having the opportunity to travel to Paris and meet with such a wide range of professionals really opened my eyes to the possibility of a career in the industry. It was reassuring to see that even after leaving academia, there is a cross-over and lots of collaboration. Industry or academia? The fork in the road when it comes to this career choice is becoming lesser and lesser.

While I was in Paris, I had a lot of time to ponder the fantastic science and research that I discussed at the talks (Did you know? One adult human heart produces enough energy in one lifetime to power an 18-wheeler to the moon and back). Additionally, I could also see first-hand that the positive aspects that we associate with academia (presenting research, freedom of research topics and the conference wine receptions, of course) are also readily available as a non-academic based scientist. In fact, there is a career that has the “goodness of both”. So many academics discussed start-ups and spin-out companies developed off the back of their academic research, and there were even talks that discussed the how, what, when and where of transitioning between the two settings.

I’m so grateful that I could attend this conference. I presented my research (a project very much blended between academia and industry), got to chat to like-minded people and came home with a wealth of new knowledge. This knowledge will not only enrich my PhD project but will stand for me as my career moves from student to fully-fledged scientist. The topic of post-PhD job hunting often comes with a knot in the stomach, but seeing the exciting opportunities that are available out there has me much more excited than stressed about this next step. And now to finish this PhD so that I can take that next step 🙂

My trip became possible thanks to the Company of Biologist travel grant and support from the RCSI Department of Anatomy and Regenerative Medicine.

Written by Ellen King

12 week research placement ends too soon

Hello everyone, I’m Amy! I joined the team for my TUD undergraduate research project in February, which is sadly coming to an end in the coming weeks. As my time here closes, I’m filled with mixed emotions. I am relieved and overjoyed to finish my thesis and see everything come together. However, I will certainly miss the team and working in the lab.
I have learnt so much from my time here. For instance, research isn’t for the faint-hearted! It is filled with hiccups and bumps in the roads and unexpected twists and turns. This means you have to be able to make decisions and revise plans quickly. For that, I have so much respect for the whole team and anyone who chooses the path of research.
I have also learnt so much about lab work and scientific writing. I was given independence throughout my work both in and out of the lab. With everyone more than willing to answer any queries I had and genuinely wanting to see me do my best.

My favourite part of this research project has been the hands-on lab work, specifically the tissue culture. I’ve been trying to perfect my assay for DNA quantification recently. This photo was taken after I’d done tons of pipetting and got a hand cramp! My results looked nice, so it was all worth it. 🙂

All in all, I am very grateful for the opportunity to work with this amazing and dedicated team. I wish them all the best with their studies and research!

Written by Amy Dunne