Sarcoma UK microscope
Principal Investigators: 

Professor Vincenzo D'Angiolella


The University of Oxford 

Award Amount: 
42 months

Cancer cells grow in an uncontrolled manner, dividing and growing without fully duplicating their genetic material. This leaves them vulnerable to breakage in a way that normal cell are not. This PhD project is looking at ways to exploit this vulnerability in osteosarcoma cells, by using drugs that increase the instability in these cancer cells and cause them to die.

Exploiting Oncogene-induced Replication stress in Osteosarcoma 

Osteosarcoma is a rare form of bone cancer that is usually treated with a combination of therapies that can include surgery, chemotherapy and radiation therapy.  Although treatment is effective for some patients, it is associated with significant side effects, and long-term survival is lower in those patients whose disease has spread throughout the body or for those whose tumours did not respond to chemotherapy.  Therefore, there is a need to develop more effective, better tolerated treatments for this disease which predominantly affects children and adolescents.

Cancer cells grow in an uncontrolled manner, growing and dividing without the typical constraints that apply to normal tissues.  For example, some tumours, including osteosarcoma can attempt to duplicate their genetic material (DNA) without having sufficient building blocks to complete the task. This leads to a situation where the genetic material is in a partially duplicated state and is vulnerable to breakage. In contrast, in normal tissues the cells only duplicate their DNA when they have sufficient resources to finish the job.

In this project we aim to exploit this vulnerable state by treating paediatric osteosarcoma cell lines with drugs that are designed to increase the instability of the partially duplicated tumour DNA causing it to break - thereby killing the tumour cells.   

The project will first focus on drugs that are already in clinical trials in other disease settings as any findings could potentially translate rapidly into clinical trials. In parallel we aim to identify new drug targets for this disease using gene-editing technology.

Project status: