Bone Cancer Research Trust Strictly Research Grant Applications - PowerPoint PPT Presentation

Bone Cancer Research Trust ‘Strictly Research’ Grant Applications 07/05/2016 BCRT 10 th Anniversary Conference CHARITABLE INCORPORATED ORGANISATION (CIO) NUMBER - 1159590

How can we improve treatment for metastatic osteosarcoma? or Does ANGPTL4 drive osteolysis, tumourigenesis and metastasis in osteosarcoma? Characterisation of a potential new therapeutic target… Dr Helen Knowles & Prof Nick Athanasou

Treatment of Osteosarcoma • Osteosarcoma is the most common primary bone cancer in children and young adults (age 10-24 years) Current treatment: 1. chemotherapy 2. surgery 3. chemotherapy The 5 year survival rate for osteosarcoma X-ray showing osteosarcoma patients is 60-75% tumour in bone

The problem with metastatic osteosarcoma… If the cancer has spread to another site, the survival rate falls as low as 15-30%. CT and PET CT scan showing lung metastasis

What affects your chances of recovery from osteosarcoma? 1. Rapid tumour growth 2. Moving out of bone 3. Causing growth of new blood vessels 4. Surviving in the blood stream 5. Invading another tissue

How could we improve survival of osteosarcoma patients?  improve survival rates  prevent progression to metastatic osteosarcoma Step 1: Find a protein that speeds up all these steps Step 2: Stop this protein from working and study the effect on disease progression

Angiopoietin-like 4 (ANGPTL4) We already know some steps that ANGPTL4 speeds up… Blood vessel growth ANGPTL4 speeds up bone digestion by osteoclasts Knowles et al (2010) FASEB J Swales et al (2014) PLoS One

Question 1: Is ANGPTL4 present in osteosarcoma tumours? Tumour Cells Bone Does the amount of ANGPTL4 relate to disease severity or survival?

Question 2: How does ANGPTL4 affect the behaviour of osteosarcoma cells? ** 1. Tumour growth osteosarcoma cells MG-63 Saos2 ANGPTL4

Question 2: How does ANGPTL4 affect the behaviour of osteosarcoma cells? 4. Surviving in the blood stream osteosarcoma cells MG-63 Saos2 attached floating ANGPTL4

Question 2: How does ANGPTL4 affect the behaviour of osteosarcoma cells? 5. Invading 24 hours another tissue osteosarcoma cells MG-63 Saos2 ANGPTL4

How will this project make a difference? Step 1: Find a protein that speeds up some (or all) of the 5 steps that cause metastatic osteosarcoma ANGPTL4: - present in osteosarcoma ( ?? ) - affects at least 3/5 steps Step 2: Stop this protein from working and study the effect on osteosarcoma Stop ANGPTL4 working and study - effects on osteosarcoma cells in the lab - effects on animal models of osteosarcoma Scientists are developing an ANGPTL4 inhibitor suitable for use in patients.

How will this project make a difference? The goal of this project is to find out if ANGPTL4 is a new drug target for osteosarcoma. In the long-term this will allow the development of new treatments that will: prevent progression to metastatic osteosarcoma and improve survival rates

Thank you Any Questions? Dr Helen Knowles and Professor Nick Athanasou