Research Impact – Bench to bedside – CDK4/6 inhibitor for prostate cancer in trial

Reported in the journal Oncogene in 2013, Professor Lisa Butler (pictured left) and collaborators, including the Centre’s Professor Wayne Tilley and senior author, Professor Karen Knudsen from the Kimmel Cancer Center, Thomas Jefferson University in USA. inhibition of the cyclin/cyclin-dependent kinase/retinoblastoma (CDK4/6) pathway that is critical for cell replication may have a role in controlling some human cancers where this pathway is amplified. Using the human prostate cancer explant model developed in the Dame Roma Mitchell Cancer Research Laboratories. The CDK4/6 inhibitor impaired the capacity of prostate cancer cells in human prostate tumours to proliferate and that this could be achieved independent of concurrent treatment with hormone-based therapy and radiotherapy.
Professor Butler now leads the Prostate Cancer Research Group at SAHMRI which focuses on therapeutics and lipids in prostate cancer.  Nearly five years later and with funding from Cancer Australia, Professor Butler and with medical oncologist Professor Lisa Horvath from the Chris O’Brien Lifehouse in NSW, are now testing the safety and potential effect of the same CDK4/6 inhibitor (ribociclib) in an early phase clinical trial in men undergoing surgery for high risk, localised prostate cancer. THese CDK4/6 inhibitors are already being used to treat women with breast cancer.
For the study, men receive 400mg of oral ribociclib daily for 21 days prior to prostate surgery.  Markers of cancer cell proliferation will be Biopsies of the prostate cancer prior to treatment and then at the time of prostatectomy will be compared for . Men are being evaluated for safety signals to ensure the drug is safe to proceed to larger studies,
It is hoped this research will help demonstrate the activity of this drug against prostate cancers, and lay the groundwork for more trials.
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