Coventry University Featured PhD Programmes
Marshall Wace LLP Featured PhD Programmes
Coventry University Featured PhD Programmes

Novel methodology to treat neuroblastoma


Department of Oncology and Metabolism

Dr H Bryant , Dr S Collis Wednesday, May 19, 2021 Competition Funded PhD Project (Students Worldwide)
Sheffield United Kingdom Biochemistry Bioinformatics Cancer Biology Molecular Biology

About the Project

Neuroblastoma is the most common solid extracranial tumour in infants and children. It represents approximately 7% of all cases of childhood cancer and results in about 15% of cancer deaths in children. Currently, 5 years overall survival of high-risk NB remains less than 50%, despite intensive high-dose multimodal treatment. Conventional therapy is now at the limits of tolerability and novel therapies targeting the molecular drivers of NB are urgently needed before survival rates can significantly improve.

Tumour-Treating Fields (TTFeilds), is a non-invasive anticancer treatment modality, that utilizes alternating electric fields at specific frequencies and intensities to selectively disrupt mitosis in cancerous cells. TTFields targets proteins crucial to the cell cycle, leading to mitotic arrest and apoptosis.  TTFields are FDA approved for use in newly diagnosed and recurrent glioblastoma multiforme (GBM). Trials in other localized solid tumors are ongoing, but no studies in neuroblastoma have been undertaken. Therefore this represents a unique and exciting opportunity to develop a truly new treatment option for children who have very few other options.

This project is a collaboration between industrial partners Novocure, Sheffield University and Sheffield Children’s hospital to investigate the use of TTFeilds in Neuroblastoma. It builds on our previous work in Neuroblastoma and our expertise in DNA damage and replication responses in cancer.

The project will involve culture of neuroblastoma cell lines, cytotoxicity assays, analysis of DNA replication and the DNA damage response pathway along with optimisation of TTFeilds methodology for neuroblastoma cells. You will be part of an interdisciplinary research team that spans chemists to clinicians working together to translate new ideas into cures.

Hear Dr Bryant talk about her Neuroblastoma research here

https://www.youtube.com/watch?v=q6hfNLGvmvc

Website: https://www.sheffield.ac.uk/medicine/people/oncology-metabolism/helen-e-bryant

Relevant publications:

George SL, Lorenzi F, King D, Hartlieb S, Campbell J, Pemberton H, Toprak UH, Barker K, Tall J, da Costa BM , van den Boogaard ML et al (2020) Therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma. EBioMedicine, 59

King D, Li XD, Almeida GS, Kwok C, Gravells P, Harrison D, Burke S, Hallsworth A, Jamin Y, George S , Robinson SP et al (2020) MYCN expression induces replication stress and sensitivity to PARP inhibition in neuroblastoma. Oncotarget, 11(23), 2141-2159.

Uri Weinberg, Novocure’s Tumor Treating Fields: Innovative brain cancer therapy with survival and safety benefits Introduction to brain cancer research at Novocure https://www.nature.com/articles/d42473-018-00156-3

Entry Requirements:

Candidates must have a first or upper second class honors degree or significant research experience.

How to apply:

Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisor in the respective box and select 'Oncology & Metabolism' as the department. Please also state your first and second choice project by entering the project tiles in the 'Research Topic' box on your application.

Enquiries:

Interested candidates should in the first instance contact Dr Helen Bryant -


Funding Notes

This studentship will be 42 months in duration and include home fee and stipend at UKRI rate. EU/Overseas candidates are welcome to apply, however they would be required to fund the fee difference.

References

1. Brodeur GM. Neuroblastoma: biological insights into a clinical enigma. Nature reviews Cancer 2003;3(3):203-16 doi 10.1038/nrc1014.
2. Maris JM. Recent advances in neuroblastoma. The New England journal of medicine 2010;362(23):2202-11 doi 10.1056/NEJMra0804577.
3. Cohn SL, Pearson AD, London WB, Monclair T, Ambros PF, Brodeur GM, et al. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2009;27(2):289-97 doi 10.1200/jco.2008.16.6785.
4. Brodeur GM, Seeger RC, Schwab M, Varmus HE, Bishop JM. Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science (New York, NY) 1984;224(4653):1121-4.
5. Seeger RC, Brodeur GM, Sather H, Dalton A, Siegel SE, Wong KY, et al. Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med 1985;313(18):1111-6 doi 10.1056/nejm198510313131802.
6. Whitfield JR, Beaulieu ME, Soucek L. Strategies to Inhibit Myc and Their Clinical Applicability. Frontiers in cell and developmental biology 2017;5:10 doi 10.3389/fcell.2017.00010.
7. King D., Li X. Dun, Almeida G. S., Kwok C., Gravells P., Harrison D., Burke S., Hallsworth A., Jamin Y., George S., Robinson S. P., Lord C. J., Poon E., et al MYCN expression induces replication stress and sensitivity to PARP inhibition in neuroblastoma. Oncotarget. 2020; 11: 2141-2159. doi.org/10.18632/oncotarget.27329
8. Otto T, Horn S, Brockmann M, Eilers U, Schüttrumpf L, Popov N, Kenney AM, Schulte JH, Beijersbergen R, Christiansen H, Berwanger B, Eilers M. Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma. Cancer Cell. 2009 Jan 6;15(1):67-78. doi: 10.1016/j.ccr.2008.12.005.
9. Mun EJ, Babiker HM, Weinberg U, Kirson ED, Von Hoff DD. Tumor-Treating Fields: A Fourth Modality in Cancer Treatment. Clin Cancer Res. 2018 Jan 15;24(2):266-275. doi: 10.1158/1078-0432.CCR-17-1117.
10. Giladi M, Munster M, Schneiderman RS, Voloshin T, Porat Y, Blat R, Zielinska-Chomej K, Hååg P, Bomzon Z, Kirson ED, Weinberg U, Viktorsson K, Lewensohn R, Palti Y. Tumor treating fields (TTFields) delay DNA damage repair following radiation treatment of glioma cells. Radiat Oncol. 2017 Dec 29;12(1):206. doi: 10.1186/s13014-017-0941-6.
Search Suggestions

Search Suggestions

Based on your current searches we recommend the following search filters.



FindAPhD. Copyright 2005-2021
All rights reserved.