A subgroup of patients with osteosarcoma could be helped by an existing drug, suggested scientists from the Wellcome Trust Sanger Institute in the U.K. 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 percent of patients with a genetic mutation, in particular growth factor signaling genes, may benefit from IGF1R inhibitors (Nat Commun 201;8:15936).

The results 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 tumors are removed. There has not been a new treatment for osteosarcoma in almost 40 years, in spite of extensive research.

In the study, scientists analyzed the genome of 112 childhood and adult tumors-double the number of tumors studied previously. In 10 percent of cases, the team discovered cancer-driving mutations in insulin-like growth factor (IGF) signaling genes.

IGF signaling genes are the target of 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.

Scientists looked for mutations in the tumors 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.

"By sequencing the whole genome of the tumors, we have unpicked the mechanism behind osteosarcoma for the first time," stated Adrienne Flanagan, MD, PhD, senior author from the Royal National Orthopaedic Hospital NHS Trust and University College London Cancer Institute. "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 tumors in children and adults, which are not the result of aging."

Peter Campbell, MD, PhD, lead author from the Wellcome Trust Sanger Institute, noted: "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' tumors 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 percent of osteosarcoma patients."