Northern Institute for Cancer Research

Neuroblastoma

Neuroblastoma

About

Our research focuses on understanding the genetic and epidemiological basis for relapsed neuroblastoma.

About

Neuroblastoma is a tumour of the sympathetic nervous system. It is the most common extracranial paediatric solid tumour. 

It is the commonest cancer of infants less than 12 months old. In the UK around 100 cases are diagnosed each year. 

Around half of all cases are low and medium risk tumours. Some of these require very little treatment to cure. 

The remainder are classified as high risk where the tumour has spread to distant metastatic sites or there is unfavourable biology. This can include amplification of the MYCN oncogene.

We work in close collaboration with colleagues in the Institute of Genetic Medicine and the Institute of Health & Society. 

We test new combinations of targeted drugs and biomarker development with colleagues in Drug Development.​

Our research

Unfortunately only around half of high risk patients can currently be cured. This is despite intensive multi-modal therapy including:

  • chemotherapy
  • surgery
  • high dose chemotherapy and autologous stem cell rescue
  • radiotherapy 
  • immunotherapy 

Our research focuses on understanding more about the biology of high risk disease. We aim to identify and develop new treatment targets and biomarkers.

Publications

Basta NO, Halliday GC, Makin G, Birch J, Feltbower R, Bown N, Elliott M, Moreno L, Barone G, Pearson AD, James PW, Tweddle DA, McNally RJ. Factors associated with recurrence and survival length following relapse in patients with neuroblastoma. Br J Cancer. 2016 Oct 4. doi: 10.1038/bjc.2016.302.

Decock A, Ongenaert M, Cannoodt R, Verniers K, De Wilde B, Laureys G, Van Roy N, Berbegall AP, Bienertova-Vasku J, Bown N, Clément N, Combaret V, Haber M, Hoyoux C, Murray J, Noguera R, Pierron G, Schleiermacher G, Schulte JH, Stallings RL, Tweddle DA; Children’s Cancer and Leukaemia Group (CCLG), De Preter K, Speleman F, Vandesompele J. Methyl-CpG-binding domain sequencing reveals a prognostic methylation signature in neuroblastoma. Oncotarget. 2016 Jan 12;7(2):1960-72.

Muirhead CR, Tweddle DA, Basta NO, McNally RJ. Temporal clustering of neuroblastic tumours in children and young adults from Northern England. Environ Health. 2015 Sep 4;14:72.

Chen L, Rousseau RF, Middleton SA, Nichols GL, Newell DR, Lunec J, Tweddle DA.
Pre-clinical evaluation of the MDM2-p53 antagonist RG7388 alone and in combination with chemotherapy in neuroblastoma. Oncotarget. 2015 Apr 30;6(12):10207-21.

Evans L, Chen L, Milazzo G, Gherardi S, Perini G, Willmore E, Newell DR, Tweddle DA. SKP2 is a direct transcriptional target of MYCN and a potential therapeutic target in neuroblastoma. Cancer Lett. 2015 Jul 10;363(1):37-4.

Defferrari R, Mazzocco K, Ambros IM, Ambros PF, Bedwell C, Beiske K, Bénard J, Berbegall AP, Bown N, Combaret V, Couturier J, Erminio G, Gambini C, Garaventa A, Gross N, Haupt R, Kohler J, Jeison M, Lunec J, Marques B, Martinsson T, Noguera R, Parodi S, Schleiermacher G, Tweddle DA, Valent A, Van Roy N, Vicha A, Villamon E, Tonini GP. Influence of segmental chromosome abnormalities on survival in children over the age of 12 months with unresectable localised peripheral neuroblastic tumours without MYCN amplification Br J Cancer. 2015 Jan 20;112(2):290-5.

Shouksmith AE, ,Evans L.E, Tweddle, DA, Miller DC, Willmore E, Newell DR, Golding BT, Griffin RJ, Synthesis and Activity of Putative Small-Molecule Inhibitors of the F-Box Protein SKP2*Australian Journal of Chemistry 2015; 68(4). DOI:10.1071/CH14586.

Chen L, Zhao Y, Halliday GC, Berry P, Rousseau RF, Middleton SA, Nichols GL, Del Bello F, Piergentili A, Newell DR, Lunec J, Tweddle DA. Structurally diverse MDM2-p53 antagonists act as modulators of MDR-1 function in neuroblastoma. Br J Cancer.Aug 12;111(4):716-25.

Bell E, Ponthan F, Whitworth C, Tweddle DA, Lunec J, Redfern CP. COX2 expression in neuroblastoma increases tumorigenicity but does not affect cell death in response to the COX2 inhibitor celecoxib. Clin Exp Metastasis. 2014 Aug;31(6):651-9.

Barone G, Tweddle DA, Shohet JM, Chesler L, Moreno L, Pearson AD, Van Maerken T (2014) MDM2-p53 interaction in paediatric solid tumours: preclinical rationale, biomarkers and resistance. Current drug targets 15(1): 114-23.

Sung PJ, Boulos N, Tilby MJ, Andrews WD, Newbold RF, Tweddle DA, Lunec J (2013) Identification and characterisation of STMN4 and ROBO2 gene involvement in neuroblastoma cell differentiation. Cancer letters 328(1): 168-75.

Chen L, Tweddle DA (2012) p53, SKP2, and DKK3 as MYCN Target Genes and Their Potential Therapeutic Significance. Frontiers in oncology 2: 173.

Cattelani S, Ferrari-Amorotti G, Galavotti S, Defferrari R, Tanno B, Cialfi S, Vergalli J, Fragliasso V, Guerzoni C, Manzotti G, Soliera AR, Menin C, Bertorelle R, McDowell HP, Inserra A, Belli ML, Varesio L, Tweddle D, Tonini GP, Altavista P, Dominici C, Raschella G, Calabretta B (2012) The p53 codon 72 Pro/Pro genotype identifies poor-prognosis neuroblastoma patients: correlation with reduced apoptosis and enhanced senescence by the p53-72P isoform. Neoplasia (New York, NY 14(7): 634-43.

Fisher JP, Tweddle DA (2012) Neonatal neuroblastoma. Seminars in fetal & neonatal medicine 17(4): 207-15.

Gamble LD, Kees UR, Tweddle DA, Lunec J (2012) MYCN sensitizes neuroblastoma to the MDM2-p53 antagonists Nutlin-3 and MI-63. Oncogene 31(6): 752-63.

 

 

Staff

Group Leader: Prof Deborah Tweddle

Post-doctoral researchers:
Dr Lindi Chen
Dr Al Gabriel

PhD student: Swathi Merugu

Academic Foundation Doctor: Dr Hayley Bowyer

Clinical Fellow: Dr Fiona Herd

Collaborators

Institute of Health & Society:
Dr Richard McNally
Mrs Nermine Basta
Prof Catherine Exeley
Ms Melissa Girling

Institute of Genetic Medicine:
Dr Nick Bown
Ms Angharad Humphreys

CCLG Staff

Director of CCLG Tumour BankProf Deborah Tweddle

Newcastle Academic Health Partners Biobank Manager: Dr Amy Peasland

Project Manager: Dr Ghada Malik

Biobank technician: Alison Page

Linked to University of Leicester

CCLG Chief Executive: Mr Ashley Gamble

Tissue bank Manager: Dr Gita Mistry

Tissue Bank Data coordinator: Mrs Caroline Ellershaw

Biological Studies Administrator:  Mrs Christine Davidson

Chair of BSSG –Dr Tom Jacques