Cancer therapy may be too targeted
Genetic landscape of rare cancer acts as a guide for future clinical trials
Researchers have identified two novel cancer genes that are associated with the development of a rare, highly aggressive, cancer of blood vessels. These genes may now act as markers for future treatments and explain why narrowly targeted therapies that are directed at just one target fail.
Angiosarcoma is a rare cancer of blood vessels. It occurs either spontaneously or can appear after radiotherapy treatment. Although quite rare, with approximately 100 people diagnosed with the cancer in the UK each year, the survival outcomes for the cancer are poorer than many other cancer types.
Scientists have previously developed drugs against angiosarcoma that target specific cellular pathways involved in the formation of blood vessels. However, these drugs have had little or no success.
In this study, the team found that 40 per cent of angiosarcomas carry mutations in genes that control blood vessel growth, including two novel cancer genes, PTPRB and PLCG1.
“Because this cancer doesn’t respond well to traditional chemotherapy and radiotherapy, it makes sense to develop drugs that target pathways that control blood vessel formation,” says Dr Peter Campbell, co-lead author from the Wellcome Trust Sanger Institute “We found two novel cancer genes that control blood vessel formation which are mutated in this cancer and which could be targeted for treatment of this highly aggressive cancer.”
However, in some patients, the team found multiple mutations in the pathway that controls blood vessel growth. These multiple mutations may make drugs developed for a single target ineffective in some patients. This study emphasises the need to take into account the effects multiple, co-operating mutations can have when designing targeted treatments for patients.
“This indicates that we may need to think more broadly to find a suitable treatment,” adds Dr Campbell.
“This study really highlights the power that a limited number of samples can have to influence the clinical and biological understanding of a rare disease, in this case angiosarcoma,” says Professor Adrian Harris, co-lead author from the University of Oxford. “Not only does our study change the way people view the biology of this tumour, it acts as a guide for future drug trials in angiosarcoma patients.”
Because so few people are affected by angiosarcoma, clinical trials can be very difficult to conduct. With this new information researchers now need to determine if existing drugs could be effective against this detrimental cancer.
“It’s extremely important to that we continue to study rare cancers such as angiosarcomas,” says Dr Sam Behjati, first author from the Wellcome Trust Sanger Institute. “Not only will this help the many patients with these cancers and improve treatment strategies, but it will help us understand the full landscape of cancer-causing mutations and the underlying biology.”
Notes to Editors
Sam Behjati, Patrick S Tarpey, Helen Sheldon et al. (2014) ‘Recurrent PTPRB and PLCG1 mutations in angiosarcoma’
Advanced online publication in Nature Genetics, 16 March. Doi: 10.1038/ng.2921
This work was supported by funding from the Wellcome Trust.
1. Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK 2. Department of Paediatrics, University of Cambridge, Hills Road, Cambridge, CB2 2XY, UK 3. The Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK 4. Human Genome Laboratory, Department of Human Genetics, VIB and KU Leuven, B-3000 Leuven, Belgium 5. Histopathology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, HA7 4LP, UK 6. University College London Cancer Institute, Huntley Street, London, WC1E 6BT, UK 7. Departments of Oncology and Genetics, Oslo University Hospital, N-0310 Oslo, Norway 8. The K.G. Jebsen Center for Breast Cancer Research, University of Oslo, N-0424 Oslo, Norway 9. Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E6BT, UK 10. Division of Molecular Structure, MRC-National Institute for Medical Research, Mill Hill, London NW7 1AA, UK 11. Department of Pathology, John Radcliffe Hospital, Oxford, OX3 9DS, UK 12. M. D. Anderson Cancer Center, The University of Texas , 1901 East Road, Houston, Texas 77054, USA 13. Bone Tumour Reference Centre, Institute of Pathology, University Hospital Basel, Basel, Institute for Applied Cancer Science, Switzerland 14. Pfizer Oncology, 10555 Science Center Dr, La Jolla, CA, 92121 15. Department of Haematology, Addenbrooke’s Hospital, Cambridge, UK 16. Department of Haematology, University of Cambridge, Hills Road, Cambridge, CB2 2XY, UK
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End of Notes to Editors
What is Angiosarcoma?
Angiosarcoma is a cancer of the inner lining of blood vessels, and it can occur in any area of the body. The disease most commonly occurs in the skin, breast, liver, spleen, and deep tissue. Angiosarcoma of the skin, or cutaneous angiosarcoma, makes up the majority of angiosarcoma cases, and it is usually found on the scalp and face. Angiosarcoma that appears underneath the surface of the skin is called subcutaneous angiosarcoma. Approximately 25% of angiosarcomas are found in deep tissue, and around 8% are found in breast tissue.
Angiosarcomas occur in men and women of all races, and they are rare in children. Patients with angiosarcoma are best treated at a cancer center where an expert sarcoma team and resources are available to provide specialized and responsive care.
What causes angiosarcoma?
In most cases, the cause of a sarcoma is unknown. The most widely known cause of angiosarcoma is lymphedema, the swelling of an area of the body due to the collection of fluid. Angiosarcoma can also occur due to radiation exposure or treatment, and angiosarcoma has been associated with carcinogens such as vinyl chloride, arsenic and thorium dioxide.
What are the symptoms of angiosarcoma?
Angiosarcoma can present in many different ways. It can look like a skin infection, a bruise or a lesion that does not heal. It may have a violet color, and one should be particularly concerned if such an area arises in a site of prior radiation therapy. It might also present as a soft lump that can be felt or seen. Deep-seated tumors may go unnoticed until they begin to affect surrounding tissues and organs.