UPDATE ON RESEARCH SUPPORTED BY TOKC
UPDATE ON RESEARCH SUPPORTED BY TOKC
December 6, 2024
Thanks to the generous support provided by Triumph Over Kid Cancer Dr. Valerae O. Lewis and her team has continued to push forward to elucidate the role of EZH2 in the progression of osteosarcoma. While COVID set back our project timeline we have continued to work towards the goal of finding novel therapeutic interventions in a disease where new treatment options are needed.
Over the past year a major milestone of the project was the submission of a manuscript detailing the results of some of these projects. The manuscript titled “Targeting IL.11R/EZH2 signaling axis as a therapeutic strategy for osteosarcoma lung metastases” was recently published in Discover Oncology. (Devarajan E, Davis RE, Beird HC, Wang WL, Jensen VB, Jayakumar A, Leung CH, Lin HY, Wu CC, Ihezie SA, Tsai JW, Futreal PA, Lewis VO. Targeting IL-11R/EZH2 signaling axis as a therapeutic strategy for osteosarcoma lung metastases. Discov Oncol. 2024 Jun 18;15(1):232). The manuscript validated interleukin-11receptor á (IL-11Rá) as a molecular target for the inhibition of osteosarcoma lung metastases. Since there is no clinically approved antibody against this receptor, we sought to identify downstream targets that mediate the effects of IL-11Rá signaling for which current drug were available (or in testing). Through manipulation of the osteosarcoma cells we identified EZH2 as a downstream candidate. We found that GSK126, EZH2 inhibitor, significantly reduced in vitro proliferation and increased cell-cycle arrest and apoptosis. In the mouse osteosarcoma model, GSK126 inhibited lung metastatic growth and prolonged survival. We then examined the osteosarcoma patient population and found that there was a significantly shorter recurrence-free survival in that IL-11Rá promotes OS lung metastasis via activation of EZH2. Thus, blocking EZH2 activity may be an effective strategy for inhibiting OS lung metastasis and improving prognosis.
We are actively collaborating with pediatric medical oncology to initiate a clinical trial and working on increasing/acquiring funding for expansion for the trial. Recent discussions with the pharmaceutical company shows promise and are allowing us to move forward with the project. With the continued help of your foundation, Dr. Lewis and team continue to move forward with the project and are excited with the progress thus far.
