Delineating the metastatic process: the role of bone cells, the cell environment and autophagy

BACKGROUND TO THE RESEARCH PROJECT
Metastatic disease is one of the major factors affecting osteosarcoma (OS) prognosis. Survival rate of patients with metastasis is 20% to 30% compared to up to 80% in non-metastatic patients. This project aims to identify how osteosarcoma cells spread to other tissues such as the lungs. Recent evidence shows that loss of a osteoclasts ((OCs); cells that break down bone) in the bone microenvironment is associated with lung metastasis.

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

BACKGROUND TO THE RESEARCH PROJECT

Current treatment for osteosarcoma relies on classical chemotherapy drugs which have significant side effects due to the fact that they also kill non-cancerous cells and patients often become resistant to the therapy meaning that they no longer work and further limiting their treatment options. 

This project aimed to find new kinder drugs that will work in osteosarcoma, even when they become resistant to the first line therapy. The objective of this study was to use high throughput Screening (HTS) to identify drug candidates effective against osteosarcoma.

Can we identify new drugs for the treatment of osteosarcoma?

BACKGROUND TO THE RESEARCH PROJECT

Osteosarcoma is the most common type of primary bone cancer affecting children and adolescents, it is a rare and often fatal disease. Historically, the overall 5-year survival rates for osteosarcoma were dire at below 20% with surgical intervention alone. The introduction of the addition of chemotherapy treatment after surgery in the 1970s radically increased rates to 50%. Since then, and the introduction of chemotherapy before surgery, the survival rate further increased to 60%. However, there has been no real advances in treatment options and the survival rates have remained poor. The 5-year survival rate is reported to be 53% for patients under 40, versus 22 % for those above. The rate is even worse for patients who present with metastatic disease at less than 30% and this has actually declined every decade, with no significant change in the survival when comparing the 21st Century figures to those from the 1970s. 

Harnessing Label-Free, Second Harmonic Generation Microscopy for Research and Diagnosis of Osteosarcoma

BACKGROUND TO THE RESEARCH PROJECT

This research project aims to introduce a new technology for the diagnosis and examination of osteosarcoma tumours. Current diagnosis of osteosarcoma is a very time-consuming process involving a number of imaging techniques and a confirmative biopsy. 

Cutting-edge laser microscopes that allow the imaging of biological samples in a non-invasive manner are being widely explored in the field of cancer research as they do not require the use of any special dyes of labels. 

This research project utilises one such laser microscope – known as second harmonic generation microscopy – being used as a new method for the diagnosis of osteosarcoma by examining abnormal collagen – a protein in our bones  which is thought to be changed drastically within bone tumours. 

Understanding how ERK5 controls osteosarcoma development and response to treatment.

BACKGROUND TO THE RESEARCH PROJECT

There is evidence from current research work undertaken in this lab that a protein called ERK5 can promote the progression of osteosarcoma. Clinical studies have also revealed a strong link between ERK5 signalling and outcomes for osteosarcoma patients.  A recent study of samples from osteosarcoma patients showed that high levels of ERK5 correlated with disease progression (87% of patients), resistance to chemotherapy (53% of patients), and was detected in 70% of metastases, where it correlated with decreased overall survival.  

Developing a 3-dimensional multicellular model of human osteosarcoma

BACKGROUND TO THE RESEARCH PROJECT

The most common bone cancer in young people is osteosarcoma. It is an aggressive cancer and unfortunately treatment hasn't progressed much in 40 years. This team at Southampton have created a laboratory model of osteosarcoma to try and better understand how this disease arises from normal bone cells and to test potential new therapies to prevent the growth of this cancer. 

The origin of osteosarcoma cells in bone is still unknown, and this lack of understanding prevents early detection of this disease. Bone grows from specialised cells located in the bone marrow (the soft, jelly-like tissue found in the centre of most bones). In Hannah’s PhD project, the team were interested to see if there were differences between the cells of the bone marrow from distinct locations of the long thigh bone and whether these differences might impact their ability to initiate disease.