Humanized models for pre-clinical osteosarcoma research

Overview

Osteosarcoma (OS) is the most commonly occurring malignant bone tumour, predominantly affecting children and adolescents. Most OS patients are treated with a combination of surgery (tumour resection) and systemic chemotherapy with Doxorubicin.

Unfortunately local recurrence and subsequent metastatic spread still frequently occurs, with an ultimate five-year survival rate of only around 25% once metastasis has occurred. There has been no progress in the enhancement of overall OS patient survival in the last four decades. One of the main reasons for this is the lack of suitable pre-clinical models to accurately recapitulate key disease process.

This project will establish a novel OS model which can assess complex surgical and therapeutic techniques. This will utilise the approach of “humanising” to engraft human tissue-engineered microenvironments for human tumour growth within an immunocompromised rat host.

Research activities

In this project, we will generate a humanized bone and OS tumour to study physiologically relevant tumour growth in an immunocompromised rat model. We'll use this model to study clinically-translatable surgical tumour resection techniques, novel local chemotherapy delivery and subsequent bone defect regeneration using customisable and biodegradable scaffolds.

The skills and techniques for this project include:

• primary human cell culture
• cancer cell line culture
• animal handling, drug delivery and surgical techniques
• xenograft models
• in vivo imaging
• tissue processing
• histology and immunohistochemistry
• data analysis and interpretation.

Outcomes

This project will pave the way to developing an effective pre-clinical model to study new drugs, drug targets, as well as drug delivery systems and complex surgical and regenerative techniques.

Skills and experience

As the ideal candidate you should be:

• interested in learning and utilising a wide range of laboratory-based techniques
• able to work in a diverse and multi-disciplinary team environment
• skilled in planning and prioritising work to meet deadlines
• experienced with pre-clinical animal models and techniques (e.g i.v, i.p. injections, surgical skills).

Keywords

• Tissue-engineering
• Bone construct
• Osteosarcoma
• Local chemotherapy
• Surgical resection

Contact

Contact Dr Jacqui Mcgovern for more information.