Psoriasis drug could treat rare bone cancer
A treatment for psoriasis could be repurposed to treat a rare but aggressive form of youth cancer, according to a new study led by the Garvan Institute of Medical Research and published in the journal Cancer Discovery.
Osteosarcoma is a rare cancer, but among the 10 most common cancers affecting males between ages 15 to 29, in Australia. Arising in bone, osteosarcoma is often dismissed as growing pain or injury, and in many cases only detected after it has spread to other parts of the body. With no real advances in treatments over the past four decades, the five-year survival rate remains as low as 65%.
“Our search for new potential treatments for osteosarcoma began in 2013 when we investigated genetic risk factors for this form of cancer,” said Garvan’s Dr Maya Kansara, first author on the study.
“From genome-wide association studies conducted with the US National Institutes of Health we saw that variants in a gene that encodes the protein GRM4 were frequently associated with osteosarcoma.
“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. In our model, we discovered that the inflammatory molecule IL23 was critical to osteosarcoma formation and progression.”
When the researchers removed IL23 in mice, they were protected from developing osteosarcomas. When they blocked IL23 in mice with existing osteosarcoma, tumour growth was slowed — and in synergism with doxorubicin, a current standard of care treatment for this form of cancer, tumour growth was even further suppressed. Analysis of human osteosarcoma biopsies confirmed that more than 70% of samples had significantly higher levels of IL23 than non-tumour tissue.
Therapies targeting IL23 have been investigated extensively for a number of autoimmune diseases, including arthritis, intestinal inflammation and the skin condition psoriasis. Drugs that block IL23 are indeed already approved and well tolerated, and on the market now for the treatment of psoriasis, noted Garvan’s Professor David Thomas, senior author on the study.
“We are now designing clinical trials to see whether they can provide much-needed improved health outcomes for osteosarcoma patients,” Prof Thomas said.
Interestingly, data from a Danish cohort study published in 2017 suggested that patients with psoriasis were almost five times more likely to develop sarcomas than individuals without the skin condition, which “reaffirms the central role IL23 plays in osteosarcoma” according to Dr Kansara. And as the expression of IL23 is higher in multiple cancer types, the researchers believe this may have broader implications for cancer outcomes.
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