Scientists from the Garvan Institute of Medical Research have recently found that a psoriasis drug may be effective in treating osteosarcoma, the most common form of bone cancer in children. Using mouse models of the disease in a preclinical study, the researchers showed that Interleukin-23 (IL-23) plays an essential role in the development of osteosarcoma. Targeting this immune molecule with the psoriasis drug led to a reduction in the osteosarcoma tumor size in mice. Their work was published on September 16 in the journal Cancer Discovery and offers hope to those suffering from osteosarcoma, being that there have been few breakthroughs in treating the condition.
“There has been no real advance in treatments for this form of cancer in four decades – we have uncovered a new target that we know can be modulated with existing therapy,” noted senior author Professor David Thomas, Garvan Cancer Research Theme Leader and Director of the Kinghorn Cancer Centre. “We hope our findings will lead to clinical trials that will provide better outcomes for patients with this rare form of cancer.”
Osteosarcoma by the Numbersttw
Osteosarcoma is a particularly rare form of cancer, affecting 3-4.5 of every 1 million patients aged 24 or younger each year, as per the World Health Organization. Despite this sparse prevalence, osteosarcoma is still the eighth most common cancer in children and adolescents and is the most commonly occurring bone cancer. The condition is often misinterpreted as growing pain or injury and can go undetected until it has begun spreading to other regions of the body. With a five-year survival rate of 65%, osteosarcoma is an aggressive form of cancer that has unmet treatment needs.
“Our search for new potential treatments for osteosarcoma began in 2013 when we investigated genetic risk factors for this form of cancer,” claimed first author Dr. Maya Kansara, who leads the Immunobiology of Cancer Group at Garvan. “From genome-wide association studies conducted with the U.S. National Institutes of Health we saw that variants in a gene that encodes the protein GRM4 were frequently associated with osteosarcoma.”
Background of the Garvan Research
Using a mouse model of the disease, Kansara and colleagues investigated the role of both GRM4 and several immune molecules that GRM4 regulates the production of. Through this work, the researchers identified IL-23, a molecule that contributes to the inflammatory response, to be pivotal in the development and progression of osteosarcoma.
When IL-23 was removed from the mice, they were unable to develop osteosarcomas. Similarly, when IL-23 was blocked in mice that had already developed osteosarcoma, the growth of the tumor slowed. When IL-23 was inhibited in this manner while the mice were given the common osteosarcoma treatment doxorubicin, the team noted this effect was even more pronounced.
Analyzing biopsies from human osteosarcoma, the researchers found that over 70% of these samples displayed significantly higher levels of IL-23 than healthy tissue. This overexpression of the inflammatory molecule is characteristic of several forms of cancer; therefore, the researchers feel these findings have implications outside of treating just osteosarcoma.
Drugs that target IL-23 have been developed and researched for several conditions, including arthritis, gastrointestinal inflammation, and psoriasis.
“Drugs that block IL23 are approved and well tolerated, and on the market now for the treatment of psoriasis,” noted Thomas. “We are now designing clinical trials to see whether they can provide much-needed improved health outcomes for osteosarcoma patients.”
A 2017 study suggested that patients with psoriasis were nearly five times as likely to develop sarcomas than their healthy counterparts, further supporting the theory that IL-23 may be a key target in combatting the cancer.
“This data reaffirms the central role IL23 plays in osteosarcoma, and that we’re on the right track,” concluded Kansara.
Re-purposing an existing drug for a different medical condition. Psoriasis drug apparently offers treatment option for osteosarcoma, a rare cancer that affects young people https://t.co/iFYAyKdxw6 via @medical_xpress
— delthia ricks 🔬 (@DelthiaRicks) September 18, 2019