5th Neuroblastoma Research Symposium, Cambridge, 11-12th April 2019

Here, we are – the Irish neuroblastoma research team landed at the 5th Neuroblastoma Research Symposium in Cambridge. Four poster presentations by four enthusiastic scientists. The two days crash course in neuroblastoma – vibrant, intense, informative.

I had one of the most enjoyable poster sessions in the last few years! A genuine interest in our 3D in vitro cancer models by both academics and Industry. Hope, to keep the ball rolling and strengthen these new links.

The Symposium programme was an excellent balance of the new transnational outcomes with hardcore developmental cellular programmes. From ‘How neuronal precursors select their fate and how they can escape the developmental constraints? How this knowledge can help to advance our understanding of neuroblastoma aetiology?’ to ‘New drugs that demonstrated great potency in pre-clinical studies’ via ‘how we can work together more efficiently to progress quicker’

Indeed, the success of the research meeting became possible thanks to the strategic vision and leadership of organisers!

Dream Team in Action: Olga, John, Ciara & Tom

SYMPOSIUM PROGRAMME
THURSDAY 11TH APRIL
12:00 – 13:00 Registration, lunch & poster setup

13:00 – 13:10 Introduction – Neuroblastoma UK & CRUK Cambridge Centre

Session 1: Neuroblastoma biology & prognosis

Cancer Research UK Cambridge Centre Neuro-oncology Programme Session

Chair: Kate Wheeler (Oxford Children’s Hospital)

13:10 – 13:40 Sandra Ackermann (Cologne): The genetic basis of favourable outcome and fatal tumour progression in neuroblastoma

13:40 – 14:10 Rogier Versteeg (Amsterdam): The dark side of neuroblastoma

14:10 – 14:40 Katleen de Preter (Ghent): Improved diagnosis and risk stratification of paediatric cancers using liquid biopsies

14:40 – 14:55 Sue Burchill (Leeds): Self-renewing neuroblastoma cells isolated from bone marrow aspirates of children with stage M disease share a mesenchymal expression signature: an NCRI CCL CSG Neuroblastoma Group Study

14:55 – 15:15 Combined discussion

15:15 – 15:45 Tea with Posters

Session 2: Targeted & combination therapy I

Cancer Research UK Cambridge Centre Neuro-oncology Programme Session

Chair: Marie Arsenian Henriksson (Karolinska)

15:45 – 16:15 Frank Westermann (Heidelberg): Novel metabolic dependencies of MYCN-driven neuroblastoma

16:15 – 16:45 Gerard Evan (Cambridge): Is Myc really master of the universe?

16:45 – 17:00 Melinda Halasz (University College Dublin): Anti-Cancer Effects of Diphenyleneiodonium Chloride (DPI) In MYCN-Amplified Neuroblastoma

17:00 – 17:15 Evon Poon (ICR, Sutton): Pharmacological blockade of high-risk MYCN driven neuroblastoma using an orally-bioavailable CDK2/9 inhibitor

17:15 – 17:35 Combined discussion

Downing College – Main Hall.jpg
17:35 – 19:15 Poster viewing & Drinks

19:30 Symposium Dinner at Downing College (map for dinner)

FRIDAY 12TH APRIL
08:30 – 08:50 Coffee & pastries

Session 3: Neural crest & differentiation therapy I

Chair: Margareta Wilhelm (Karolinska)

08:50 – 09:20 Igor Adameyko (Karolinska): Normal development of sympathoadrenal system resolved with lineage tracing and single cell transcriptomics

09:20 – 09:50 Quenten Schwarz (Adelaide): Guiding sympathoadrenal neural crest cells to the adrenal primordia

09:50 – 10:05 Claudia Linker (King’s College London): Notch coordinates cell cycle progression and migratory behaviour leading to collective cell migration

10:05 – 10:20 Combined discussion

10:20 – 10:50 Coffee with Posters

Session 4: Neural crest & differentiation therapy II

Chair: Gareth Evans (York)

10:50 – 11:20 Karen Liu (King’s College London): ALK and GSK3 – shared features of neuroblastoma and neural crest

11:20 – 11:35 Anestis Tsakiridis (Sheffield): Efficient generation of trunk neural crest and sympathetic neurons from human pluripotent stem cells via a neuromesodermal progenitor intermediate

11:35 – 12:05 Anna Philpott (Cambridge): Using developmental mechanisms to drive differentiation of neuroblastoma

12:05 – 12:20 Combined discussion

12:20 – 13:20 Lunch with Posters

Session 5: Targeted & combination therapy II

Chair: Bengt Hallberg (Gothenburg)

Cancer Research UK Cambridge Centre Paediatrics Programme Lecture:

13:20 – 13:50 Sharon Diskin (Philadelphia): A multi-omic surfaceome study identifies DLK1 as a candidate oncoprotein and immunotherapeutic target in neuroblastoma

13:50 – 14:05 Donne Nile (Glasgow): Manipulation of cancer cell metabolism for neuroblastoma combination therapy with targeted radiotherapy

14:05 – 14:35 Suzanne Turner (Cambridge): CRISPR-dCas9 screens to identify resistance mechanisms to ALK in neuroblastoma

14:35 – 14:50 Combined discussion

14:50 – 15:20 Tea with Posters

15:20 – 15:30 Poster prizes

Session 6: Targeted & combination therapy III

Chair: John Lunec (Newcastle)

15:30 – 16:00 Per Kogner (Karolinska): The PPM1D encoded WIP1 phosphatase is an oncogene significant for cancer development and tumour progression and a druggable therapy target in neuroblastoma and medulloblastoma. A hint as to how aggressive childhood cancer manages with wild-type p53

16:00 – 16:15 Deb Tweddle (Newcastle): Preclinical assessment of MDM2/p53, ALK and MEK inhibitor combinations in neuroblastoma

16:15 – 16:30 Sally George (ICR, Sutton): A CRISPR-Cas9 genomic editing and compound screening approach identifies therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma

16:30 – 16:45 Miriam Rosenberg (Jerusalem): Expression- and immune-profiling of neuroblastoma-associated Opsoclonus Myoclonus Ataxia Syndrome (OMAS) to identify features of auto- and tumour-immunity

16:45 – 17:00 Combined discussion

17:00 Close

SFI Technology Innovation Development Award

An interesting idea or research question is always motivational. But it is a sketch till you get means to answer them. We, scientists, have to shape them into a proposal showing that we know limitations and have plans B & C if things go differently to planned. Then we apply for funding here and there… and many many times. The number of rejections makes us stronger – I hope. But one day, the idea may hit it right. So, it has happened to me recently and this SFI Award brings so needed fuel to study neuroblastoma.

The development and approval of new oncology drugs are very slow processes. This is mainly due to the big differences in the physiology of cancer cells grown on plastic and in the native microenvironment. Tissue engineering of tumour systems has a great potential to bridge this gap. This Award will help to advance our 3D tissue-engineered of neuroblastoma, that can be used in testing new drugs and new combinations of existing drugs.

Neuroblastoma cells grown in 3D

In particular, we will adapt the 3D model to screen different immunotherapies. This treatment option is very attractive both for adults and children because of its specificity and reduced side effects compared to chemotherapy, the current standard of care.

This Award will help my team to get a better understanding how neuroblastoma cells interact with the body environment, particularly with the immune system and how we can use the knowledge to develop new treatments and improve the patient outlook.

Every child deserves a happy childhood

Three girls fountain in Mainz Germany

Last year I have selected this photo of a lovely fountain capturing 3 girls under umbrellas (Drei-Mädchen-Brunnen) in Ballplatz Mainz in support of #ChildhoodCancerAwarnessMonth. This fountain was built between two Catholic girl’s schools symbolising the separate education and a happy childhood. It is charming on its own. And I’ve select it again.
Every child deserves a happy childhood. Raising awareness about childhood cancer we help to make the dreams of children with cancer come true. Dreams for a happy childhood, better treatment, better quality of life full of love ahead through better funding of childhood cancer research and access to innovative treatments.

September is Childhood Cancer Awareness Month!

Today marks the start of Childhood Cancer Awareness Month.

Three girls fountain in Mainz Germany 

The cause of childhood cancers is believed to be due to faulty genes in stem cells that give rise to nerves, skin, blood and other body tissues. For some unknown reasons, the faulty genes can sit quiet and show their ‘bad’ character after birth and programme the cells into cancer cells.
So, there is no evidence that links lifestyle or environmental risk factors to the development of childhood cancer, which is opposite to many adult’s cancers.

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

Children are not little adults and so their cancer. Some childhood cancers have a good outlook and successful protocol of treatments. However, some of the cancers do not respond to the known drugs, or if respond cancer cells find the way to develop resistance and come back being more aggressive. Among theme are some forms of brain tumours, neuroblastoma and sarcomas; cancers developing in certain age groups and/or located within certain sites in the body, along with acute myeloid leukaemia (blood cancer). Children with a rare brain cancer – diffuse intrinsic pontine glioma survive less than 1 year from diagnosis. Children with soft tissue tumours have 5-year survival rates ranging from 64% (rhabdomyosarcoma) to 72% (Ewing sarcoma). Less than50% of children with the aggressive form of neuroblastoma will live beyond 5 years with current treatment strategies.

For majority of children who do survive cancer, the battle is never over. Over 60% of long‐term childhood cancer survivors have a chronic illness as a consequence of the treatment; over 25% have a severe or life-threatening illness.

The most common types of childhood cancer are:

  • Leukaemia and lymphoma (blood cancers)
  • Brain and other central nervous system tumours
  • Muscle cancer (rhabdomyosarcoma)
  • Kidney cancer (Wilms tumour)
  • Neuroblastoma (tumour of the non-central nervous system)
  • Bone cancer (osteosarcoma)
  • Testicular and ovarian tumours (gonadal germ cell tumours)

Please see a short video The Childhood Cancer Ripple Effect created by St. Baldrick’s Foundation.

Irish Neuroblastoma Research Collaboration

On November 20th, the Irish neuroblastoma researchers have met for the first time to set up a collaborative research hub.  The aim is to consolidate their expertise and skills in order to crack the neuroblastoma code together.

They all have different science background spanning from molecular and cellular biologists,  immunologists, tissue-engineering, bioinformatics, mathematical modelling and clinicians representing RCSI, UCD, TCD, OLCHC and NCRC. During this meeting, researchers talked about their challenges and progress finding out that we are complementing each other projects. Clinicians from different OLCHC departments exposed basic researchers to realities of the disease.  None would find this information in academic papers: it is what you see in the clinic and how it works in practice.

Big thank you to Dr Cormac Owens for the invitation and linking us together and Prof Jacinta Kelly for mapping the support available from the NCRC and CMRF.

Our next meeting will be held in RCSI in January 2018.

Happy Birthday the Irish Neuroblastoma Research Consortium!

 

 

 

 

 

 

The Puzzle of Childhood Cancer Research

We hear great news from the US labs that a new treatment is on the way for children with cancer. Most of their research is funded by charities and success stories appear because of the people who want to make dreams come true for kids with cancer and their families. Dreams for longer and healthier life.

Interestingly, the study led by Professor Bernie Hannigan, the University of Ulster, which was published by Medical Research Charities Group, identified main gaps that keep Ireland at the bay:

Generosity of Pixabay

  • Childhood cancer research areas are not prioritised, including neuroblastoma.
  • No Government funding support for childhood cancer research. The research has to compete on general terms with well-funded research groups/centres/clusters focused on the adult cancers (breast, prostate, etc)
  • No systematic involvement in research of Patients or other lay people.
  • No medical research charities to fill the gap in childhood cancer research funding.

The good news: that things are changing thanks to The Conor Foley Neuroblastoma Cancer Research Foundation and Lightitupgold Childhood Cancer Foundation. Some childhood cancer research is funded by Children’s Medical and Research Foundation. But this research field needs more.
#ChildhoodCancerAwarenessMonth

MRCG_Research_Report

Irish Neuroblastoma Research Charity

Continuing the fundraising theme, I would like to introduce The Conor Foley Neuroblastoma Cancer Research Foundation. It is founded by the family aiming to raise awareness and funding for neuroblastoma – one of the most aggressive childhood cancer.  This charity is being driven by parents who lost their son to neuroblastoma. They want to fill this gap as well as bring attention to the lack of funding for childhood cancer research.

Their son Conor was diagnosed with neuroblastoma at the age of four. He was a teenager when he relapsed. He had been 10 years cancer-free. After all possible treatments, neuroblastoma took over.

His mom Margaret says:

“We always dealt with Conor’s illness privately. There were no Facebook pages tracking Conor’s progress. The day we launched the website for Conor’s charity was very emotional for me. I feel like he is out there now in the big world now with his charity. He will never get to do the things that most 18-year-olds do. He won’t go inter-railing in the summer, he’ll never go bungee jumping off some bridge, but I feel that he’s part of the world, doing something good for other children and their families. We valued our time with Conor so much, we want to help researchers who will give families, even more time, more options, perhaps even a cure for their children when they get the same awful news that we did. I think he would approve of that.”

The Foleys

We are continuing Conor’s legacy in removing and breaking down medical science barriers, and we have set up this foundation with the ultimate objective of finding a cure for NBL.Our aim is to secure continuous annual funding for NBL research in Ireland. With this funding we want to help develop an NBL research consortium to link with international research groups and collaborations.

 

Fundraising for Childhood Cancer Research

Dedicating posts to neuroblastoma and childhood cancer awareness month, it is impossible to stay distant about the need of fundraising to fund research. The #ChildhoodCancerAwareness Campaign aims not only attract our attention to the fact that kids get cancer too, but mostly to show how little is done to understand the causes of the disease and offer effective treatments.

  • To address the last problems more research is needed both curiosity-driven and translationally focused. To answer the question why research needs more funding, in general, you can find here.
  • Effective treatments cost money: only 4% of research funding goes to research in ALL childhood health conditions. In the other words, every 4 cents of each 1 euro are to be used in research.
  • The causes of childhood cancer including neuroblastoma are not known. It would be right to expect more blind alleys and failed ideas in the understanding these cancers.
  • The research can take decades, so it is a long-term investment. In contrary, people, who can give money (the politicians and governments), have 4-5 years of political power. 4-5 years vs decades = the discovery research becomes critically underfunded.
  • Who can change the situation? You, me and anyone. People who care. It happens through their active position and fundraising. Like the Foleys, Childhood Cancer Foundation and the Children’s Medical and Research Foundation.
  • Fundraising creates opportunities for blue sky research and developing cancer treatments.

If plants can grow through stones, so we can make a change.

 

 

Thank you all who support cancer research charities!

 

Why do we need fundraising for cancer research?

Childhood and Cancer

Walking in Mainz last week I saw a lovely fountain capturing 3 girls under umbrellas (Drei-Mädchen-Brunnen) at the ball square. This fountain was built between two Catholic girl’s schools symbolising the separate education and happy childhood. It has charmed me and reminded rainy days in Ireland and how this fountain may fit any park or square in Dublin.

My second look at the picture gave me another perspective. This sculpture could illustrate not only happy childhood but also the protection we can give to children with cancer being their umbrellas. As September is childhood cancer awareness month, I am picking this picture to support this call. Raising awareness about childhood cancer we help to make their dreams come true. Dreams for better treatment, better quality of life full of love ahead through better funding of childhood cancer research and access to innovative treatments.

Three girls fountain in Mainz Germany

What lessons have been learnt?

Today is the final day of the Third International Cancer lmmunotherapy Conference. The meeting was run at the Rheingoldhalle Congress Center in Mainz/Frankfurt, Germany from September 6-9, 2017. More than 500 people attended this meeting.

The focus of the scientific program was on “Translating Science into Survival”. Talks covered the challenging areas in cancer immunology and immunotherapy. The full list of topics can be found in the meeting program.

At the moment cancer immunology and immunotherapy is a hot topic in the next generation of anti-cancer therapies. Lots of attention is given to checkpoint immunodrugs as it was proven by the prevalence of talks on this subject in the program. Indeed, this drug has great potential, but at the same time, it is not universal. About 50% of patients do not benefit from it.

What lessons have been learned from the talks:

  • Checkpoint immunotherapies are the main stream
  • Not all cancer patients would respond to immunodrug
  • Genetic landscape of a tumour and/or the patient may contribute to this, thus making beneficial to check genetics for this type of treatment
  • Immunodrugs work better in combination with conventional therapies such as chemotherapy.
  • The immune system can be tuned by a drug, but it will switch on compensatory mechanisms to balance the intervention.
  • Lots have to be studied further