New research suggests a subset of bone cancer patients are likely to respond to IGF1R inhibitors based on their genetic profile.
A subgroup of patients with osteosarcoma 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 in the journal 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.

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.

“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,” said Dr Sam Behjati, first author from the Wellcome Trust Sanger Institute and University of Cambridge 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.