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
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
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.
Interested candidates should in the first instance contact Dr Helen Bryant - email@example.com
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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.
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