Studying angiosarcoma in dogs Dr Robin Young Consultant Medical Oncologist Sheffield Cancer Research Centre

Overview SarcomaUK funded project 2012/13 ‘Studies in angiosarcoma using canine tumours’ 1. What made you decide to research into Sarcoma? 2. How did you arrive at your research question? 3. What has your research shown? 4. How will this benefit patients?

Angiosarcoma Subtype of soft tissue sarcoma Rare, aggressive vascular tumour (tumour of blood vessels) Can develop anywhere. Most commonly: Scalp in older white males Secondary tumours in women previously treated for breast cancer with radiotherapy Treatments for angiosarcoma include surgery, radiotherapy and chemotherapy, but often treatment is very challenging

Angiosarcoma Advances in the treatment of angiosarcoma have been limited by its rarity. Few models of human angiosarcoma for laboratory research Comparative oncology Study of cancer in other species Bone cancer in dogs (Osteosarcoma) Mifamurtide Canine angiosarcoma

Studies in angiosarcoma using canine tumours

1. What made you decide to research into Sarcoma? 2006 – commenced specialist training in medical oncology at Weston Park Hospital, Sheffield 2009-2012 – YCR clinical research fellow ‘Vascular targeted agents for the treatment of angiosarcoma’ 2013 – Clinical lecturer in medical oncology 2015 – Consultant medical oncologist specialising in sarcoma, Sheffield

2. How did you arrive at your research question? 3 year YCR clinical research fellowship Tumour Microcirculation Research Group, University of Sheffield Supervisors: Prof Penella Woll – sarcoma Prof Nicola Brown – vascular biology

2. How did you arrive at your research question? In 1971, Judah Folkman reported that cancers are dependent upon a blood supply for tumour growth and spread. Drugs that target the tumour blood supply represent potential therapy for cancer (vascular targeting agents). Bevacizumab (Avastin)

2. How did you arrive at your research question? Angiosarcomas are vascular tumours ?angiosarcoma response to vascular targeting agents Axitinib – oral tablet vascular targeting agent Axi-STS – a UK, early clinical trial, led by Prof Woll, of Axitinib for advanced soft tissue sarcoma, including angiosarcoma

2. How did you arrive at your research question? YCR clinical research fellowship Laboratory studies Analysing a panel of human vascular tumour samples (haemangiomas, angiosarcomas) Studying the response of 2 human angiosarcoma cell lines to vascular targeted agents in different assays (proliferation, differentiation, migration, invasion)

2. How did you arrive at your research question? Vadimezan Potentially interesting results, particularly with a class of agents called vascular disrupting agents

2. How did you arrive at your research question? 2 human angiosarcoma cell lines No in vivo model of human angiosarcoma How to take this research forward?

2. How did you arrive at your research question? Connective Tissue Oncology Society Annual Meeting 2010 Dr Nick Duesbery Van Andel Research Institute, Grand Rapids, USA British Sarcoma Group Annual Meeting 2011 Dr Sue Murphy Animal Health Trust, Cambridge, UK

2. How did you arrive at your research question? Human angiosarcoma Canine angiosarcoma Morphology similar Aggressive tumours Rare Common (German Shepherds) Primary Secondary Cutaneous Visceral

3. What has your research shown? ‘Studies in angiosarcoma using canine tumours’ Aims: To analyse a large panel of canine angiosarcoma tumour samples using PCR, to quantify their expression of vascular growth factors. To assess the response of canine angiosarcoma cell lines to vascular targeted therapy. To compare the results with our studies of human angiosarcoma.

3. What has your research shown? Canine angiosarcoma is a useful model for studying human angiosarcoma.

4. How will this benefit patients? Clinical trial with the Animal Health Trust of a Vascular Disrupting Agent for canine angiosarcoma patients? A potential way of informing a clinical trial in human patients?

4. How will this benefit patients?

4. How will this benefit patients? Currently undertaking laboratory studies using human angiosarcoma cell lines to validate the findings from the studies at VARI of canine angiosarcoma cell lines. Collect data to support a proposal for an early phase clinical trial of combination therapy for the treatment of angiosarcoma in human patients.

Thankyou! Professor Penella Woll Professor Nicola Brown Dr Malee Fernando Dr Sue Murphy Dr Nick Duesbery