Using a mouse model, researchers have discovered a potential therapeutic target for osteosarcoma – one which is already used to treat psoriasis. These new findings are published in Cancer Discovery.
Not just "growing pains"
Osteosarcoma is a type of bone cancer, commonly diagnosed in young people; around half of new cases in the United States each year are in children and teenagers. As such, the signs and symptoms can often be mistaken for "growing pains", which can delay diagnosis. If, by this point, the cancer has spread outside the bone, five-year survival rates decrease from 77% to 65%.
Current treatment for osteosarcoma follows a standard pattern; surgery, chemotherapy and/or radiotherapy. Given the survival rate, there are efforts to develop treatments beyond this standard. One such treatment is immunotherapy, which is rapidly becoming the “fifth pillar” of cancer treatment.1
The role of the immune system
Researchers were led towards immune molecules by the results of genome-wide association studies (GWAS), which associated the gene GRM4 with susceptibility to osteosarcoma.2,3 It was through investigating this gene that they found an association between osteosarcoma and IL-23, a pro-inflammatory molecule within the immune system.
In a recent press release, lead author Maya Kansara says : "In a mouse model of osteosarcoma, we investigated the role of GRM4, as well as a number of immune molecules, the production of which is regulated by GRM4," she continues: "In our model, we discovered that the inflammatory molecule IL-23 was critical to osteosarcoma formation and progression."
The authors uncovered the role of IL-23 by removing it from mice, via a gene knock-out, finding that they were then protected from developing osteosarcomas. Blocking IL-23 in mice with existing osteosarcomas was also trialed – the growth of these tumors was successfully suppressed.4
From bench to bedside
The relationship between IL-23 and development of osteosarcoma suggests the former could be targeted in treatment of the latter. IL-23 is already a target in the treatment of some autoimmune diseases, including psoriasis.
"Drugs that block IL-23 are approved and well-tolerated, and on the market now for the treatment of psoriasis," says Professor David Thomas, co-author of the study. "We are now designing clinical trials to see whether they can provide much-needed improved health outcomes for osteosarcoma patients."
1. Oiseth, S.J., Aziz, M.S. (2017) Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead. Journal of Cancer Metastasis and Treatment. DOI: https://doi.org/10.20517/2394-4722.2017.41
2. Savage, S.A., et al. (2013) Genome-wide association study identifies two susceptibility loci for osteosarcoma. Nature Genetics. DOI: https://dx.doi.org/10.1038%2Fng.2645
3. Jiang, C., et al. (2014) GRM4 gene polymorphism is associated with susceptibility and prognosis of osteosarcoma in a Chinese Han population. Medical Oncology. DOI: https://doi.org/10.1007/s12032-014-0050-4
4. Kansara, M., et al. (2019) Infiltrating myeloid cells drive osteosarcoma progression via GRM4 regulation of IL23. Cancer Discovery. DOI: https://doi.org/10.1158/2159-8290.CD-19-0154