A subgroup of patients with osteosarcoma - a form of bone cancer - could be helped by an existing drug, suggest scientists from the Wellcome Trust Sanger Institute and their collaborators at University College London Cancer Institute and the Royal National Orthopaedic Hospital NHS Trust. In the largest genetic sequencing study of osteosarcoma to date, scientists discovered that 10 per cent of patients with a genetic mutation in particular growth factor signalling genes may benefit from existing drugs, known as IGF1R inhibitors.
The results, published today (23 June) in Nature Communications suggest a re-trial of IGF1R inhibitors for the subset of patients with osteosarcoma who are likely to respond based on their genetic profile.
Osteosarcoma is the most common form of primary bone cancer in children and young adults, usually affecting people aged 10 to 24 years*. 160 new patients are diagnosed with osteosarcoma in the UK each year, of which around one third cannot be cured.
The current treatment for osteosarcoma is chemotherapy followed by surgery, where the bone tumours are removed. There has not been a new treatment for osteosarcoma in almost 40 years, in spite of extensive research.
In the study, scientists analysed the genome of 112 childhood and adult tumours - double the number of tumours studied previously. In 10 per cent of cases, the team discovered cancer-driving mutations in insulin-like growth factor (IGF) signalling genes.
IGF signalling plays a major role in bone growth and development during puberty. Researchers believe that IGF signalling is also implicated in the uncontrollable growth of bone that is characteristic of osteosarcoma.
IGF signalling genes are the target of existing drugs, known as IGF1R inhibitors. Past clinical trials of IGF1R inhibitors as a treatment for osteosarcoma yielded mixed results although occasional patients responded to the treatment. In spite of this, IGF1R inhibitors have not been further tested in osteosarcoma, as it had been unclear who would benefit from the treatment.
Dr Sam Behjati, first author from the Wellcome Trust Sanger Institute and University of Cambridge, said: "Osteosarcoma is difficult to treat. Despite extensive research over the past 40 years, no new treatment options have been found. In this study we reveal a clear biological target for osteosarcoma that can be reached with existing drugs."
In the study, scientists looked for mutations in the tumours to understand the mechanism of osteosarcoma development. The genetic information revealed a specific process for rearranging the chromosomes that results in several cancer-driving mutations at once.
Professor Adrienne Flanagan, senior author from the Royal National Orthopaedic Hospital NHS Trust and University College London Cancer Institute, said: "By sequencing the whole genome of the tumours, we have unpicked the mechanism behind osteosarcoma for the first time. We discovered a new process -- chromothripsis amplification - in which the chromosome is shattered, multiplied and rejigged to generate multiple cancer-driving mutations at the same time. We believe this is why we see very similar osteosarcoma tumours in children and adults, which are not the result of ageing."
Dr Peter Campbell, lead author from the Wellcome Trust Sanger Institute, said: "Currently, there are no new osteosarcoma treatments on the horizon. Genomic sequencing has provided the evidence needed to revisit clinical trials of IGF1R inhibitors for the subset of patients that responded in the past. The mutations of patients' tumours may enable clinicians to predict who will, and will not respond to these drugs, resulting in more efficient clinical trials. The drugs could be effective for 10 per cent of osteosarcoma patients."
Notes to Editors
Almost all -- 94 per cent -- of osteosarcomas start in the long bones of the arms and legs, including the lower thigh bone (distal femur), upper shin bone (proximal tibia) and upper arm bone (proximal humerus). It is an aggressive cancer that can spread in the bloodstream to the lungs, where it forms bony nodules that must be detected and cut out by hand.
*Bone Cancer Research Trust: http://www.bcrt.org.uk/information/information-by-type/osteosarcoma/
For more information about osteosarcoma, please visit the Bone Cancer Research Trust website (http://www.bcrt.org.uk/)
If you'd like to speak to someone about osteosarcoma, please contact the Sarcoma UK Support Line Nurses on 0808 801 0401 or email email@example.com. For more information visit the Sarcoma UK website (http://www.sarcoma.org.uk/)
Sam Behjati et al. (2017) Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma. Nature Communications. DOI: ncomms15936
The University of Cambridge
The mission of the University of Cambridge is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. To date, 96 affiliates of the University have won the Nobel Prize. Founded in 1209, the University comprises 31 autonomous Colleges, which admit undergraduates and provide small-group tuition, and 150 departments, faculties and institutions. Cambridge is a global university. Its 19,000 student body includes 3,700 international students from 120 countries. Cambridge researchers collaborate with colleagues worldwide, and the University has established larger-scale partnerships in Asia, Africa and America. The University sits at the heart of one of the world's largest technology clusters. The 'Cambridge Phenomenon' has created 1,500 hi-tech companies, 14 of them valued at over US$1 billion and two at over US$10 billion. Cambridge promotes the interface between academia and business, and has a global reputation for innovation. http://www.cam.ac.uk/
Royal National Orthopaedic Hospital NHS Trust
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The Bone Cancer Research Trust is the leading charity dedicated to fighting primary bone cancer. The charity's mission is to save lives and improve outcomes for people affected by primary bone cancer through research, information, awareness and support. http://www.bcrt.org.uk
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The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. http://www.sanger.ac.uk
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