The drugs don’t work for the primary bone cancer osteosarcoma - finding out why and new ones that do!

Osteosarcoma is the most frequent of all primary cancers of bone and mainly affects young people with a peak of incidence at 18 years. The treatment for osteosarcoma hasn’t changed much since the 1970’s and combines surgery (often amputation) with extended courses of chemotherapy. The overall relative 5-year survival rate of patients with osteosarcoma is 70% if the tumour is localised, however this is reduced to 30% with non-localised disease (mainly lung metastases). As many patients present late with primary bone cancer, non-localised disease means many patients undergo many rounds of brutal chemotherapy treatment to no avail. The main explanation for this poor response is thought to be the development of chemoresistance which can be explained by the emergence of selected resistant cell clones, by molecular modifications of cancer cells under drug pressure and/or by the modification of the tumour microenvironment. The unsatisfactory outcomes for osteosarcoma patients and the resistance to chemotherapeutic agents both highlight the urgency of finding novel therapeutic strategies to improve the survival rates of osteosarcoma patients. In this context, there is a real need to better understand the chemoresistance-related mechanisms and to identify new therapeutic targets of the drug resistance.

This PhD project will involve the use of use ‘High throughput screening"" or HTS, of compound ""libraries"" to identify whether existing drugs can be used in osteosarcoma. Commercially available libraries will be used to enable the rapid screening of over 4400 drugs and compound in vitro. In addition, next generation sequencing and bioinformatics will be used to try and decipher the mechanisms of chemoresistance.

This project is funded by Hannah’s Willberry Wonder Pony Charity (see https://www.willberrywonderpony.org/ for more info) and is part of a larger programme of research involving a PostDoc and BMedSci the successful student would work alongside.

The successful applicant will join the Gartland Lab – headed by Professor Alison Gartland ( see https://www.sheffield.ac.uk/oncology-metabolism/staff/gartland, https://gartlandlab.com/ and https://twitter.com/ProfAllieG ). Prof Gartland is passionate about about providing projects that give students a true experience of medical research and provide a sound foundation for their future career development. During the course of the PhD, students will be given the opportunity to be involved in public engagement, teaching and attendance at both national and international conferences. The University of Sheffield also provides an excellent Doctoral Development programme (https://www.sheffield.ac.uk/rs/ddpportal/about ) to enable doctoral researchers to acquire the necessary skills and training to become world-class researcher. This is also complemented by the award winning Think Ahead programme (https://www.sheffield.ac.uk/faculty/medicine-dentistry-health/thinkahead/ta) of activities for early career researchers.

Informal enquires should be directed to Prof Gartland ([Email Address Removed]) and for information about doing a PhD project on osteosarcoma in the Gartland Lab please check out https://www.instagram.com/lukeslabbible