Reducing the burden of skin toxicity in children receiving targeted immunotherapy for neurofibromatosis Type 1 (NF1)
About the Project
Neurofibromatosis 1 (NF1) is an inherited neurocutaneous disease that predisposes affected individuals to the development of benign and malignant tumours. The disease mainly involves the skin and nervous system but people with NF1 can develop a wide range of complications. Immunotherapy with selumetinib, a mitogen-activated extracellular signal-regulated kinase (MEK)-1/2 inhibitor, has shown promising results in treating inoperable plexiform neurofibromas, with clinical trials demonstrating tumour volume reduction and improved patient-reported outcomes. However, skin toxicity is a common complication of treatment which, due to its severity, often requires interruption of therapy and this can be life limiting for these children and their families.
The Complex NF1 service, Manchester, is one of two highly specialist centres in the UK which was nationally commissioned to provide a holistic state of the art service for all complex NF1 patients through multidisciplinary expertise. In 2022, the Manchester Complex NF1 service pioneered a clinical service (still the only one if its kind in the UK) combining dermatology, oncology and neurology care for children, receiving immunotherapy for NF1, to mitigate the impact of treatment-induced skin toxicity.
Based at The University of Manchester, this project draws on a world-class dermatology clinical and research centre, co-located with a major NF1 centre of excellence, to facilitate the PhD researcher:
- Comprehensively mapping the profile of MEK inhibitor exposure and clinical response in conjunction with patient factors to understand which patient / disease characteristics predict the nature and burden of skin toxicities observed.
- Establishing whether skin toxicity be prevented and whether taking a prophylactic or reactive approach offers greater efficacy
- Determining which treatment strategy, for established skin toxicities, is most efficacious.
This project offers immediate translational potential and will enable an evidence-based approach to provide uninterrupted life-saving treatment for children with symptomatic/inoperable plexiform tumours.
Eligibility
Applicants are expected to hold (or about to obtain) a minimum upper second-class undergraduate honours degree (or equivalent) in biochemistry or related subject area. Experience of working with children / children with special educational needs and disabilities is desirable.
How to Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Interested candidates must first make contact with the Primary Supervisor prior to submitting a formal application, to discuss their interest and suitability for the project. On the online application form select PhD Dermatological Sciences.
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