Despite extensive research, there have been no new treatments in nearly 40 years for osteosarcoma.
Scientists have identified a clear biological target for the treatment of osteosarcoma that can be hit with existing drugs.
In a study published in Nature Communications, investigators found that 10% of patients with a genetic mutation in insulin-like growth factor (IGF) signaling genes may benefit from treatment with IGF1R inhibitors.
Osteosarcoma is a primary malignancy of bone that typically affects children and adults aged 10 to 30 years—–although teens are the most commonly affected. According to the American Cancer Society, approximately 1000 new cases of osteosarcoma are diagnosed per year in the United States, of whom, 450 are children and teenagers.
For the study, investigators analyzed the genome of 112 childhood and adult tumors that encompassed all major histological subtypes. They found that 10% of cases had cancer-driving mutations within IGF signaling genes.
IGF signaling plays an important role in childhood growth and continues to have anabolic effects in adults. Scientists believe that it may also play a role in the uncontrollable growth of bone, a characteristic of osteosarcoma.
The standard treatment for osteosarcoma is chemotherapy followed by surgery. No new treatments have been developed for the disease in nearly 40 years.
Past clinical trials of IGF1R inhibitors have been conducted for the treatment of osteosarcoma, but the data have yielded mixed results. Although some patients did occasionally respond to treatment, these inhibitors have not been further examined in osteosarcoma.
“Osteosarcoma is difficult to treat,” said first author Dr Sam Behjati. “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.”
A key finding of the study showed potentially actionable somatic alterations in IGF signaling genes in a subset of cases.
“Furthermore, we describe a distinct pattern of genomic rearrangement, chromothripsis amplification, that generates driver mutations across the osteosarcoma genome,” the authors wrote.
This process results in several cancer-driving mutations at once, according to the authors.
“By sequencing the whole genome of the tumors, we have unpicked the mechanism behind osteosarcoma for the first time,” said senior author Adrienne Flanagan. “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.”
The authors noted that this process may be why similar osteosarcoma tumors are observed in children and adults, which are not the result of aging.
“Currently, there are no new osteosarcoma treatments on the horizon,” said lead author Dr Peter Campbell. “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% of osteosarcoma patients.”