Ezrin Inhibitors for the Treatment of Cancer
Categories: “Cancer Therapeutics“
Reference #: 2010-037
Most localized tumors can be treated by surgery or chemotherapy, but metastasis is a major clinical problem in current cancer therapy. Metastasis of osteosarcoma (OS) to lungs is an early process and present in patients even with localized appearing tumors. Ezrin is a critical protein in metastasis of OS and various other tumor types. Expression of ezrin correlates with high metastatic potential and poor survival in human, dog and mouse OS tumors. Thus, ezrin is a validated molecular target for the prevention and treatment of cancer metastasis in multiple tumor types. The present invention describes compounds that specifically bind to ezrin and prevent tumor metastasis growth. The invention also has potential applications for other pediatric cancers including rhabdomyosarcoma.
Potential therapeutic agent for the treatment of metastatic OS and multiple cancers including pancreatic cancer, ovarian cancer and rhabdomyosarcoma.
- Targeted therapy for the treatment of metastatic OS; potentially advantageous over conventional approaches of surgery and chemotherapy.
- Benefit of reduced toxicity comparable to traditional chemotherapeutic methods.
Stage of Development
Researchers have identified lead compounds that specifically inhibit lung metastasis of ezrin sensitive but not ezrin-resistant cells in vivo.
These compounds have been tested for toxicity and PK and PD studies are ongoing. Researchers have also identified the molecular mechanism of these ezrin inhibitors.
“Small molecule inhibitors of ezrin inhibit the invasive phenotype of osteosarcoma cells”. Bulut G. et al., Oncogene, 2012 Jan 19;31(3):269-81.
“The ezrin metastatic phenotype is associated with the initiation of protein translation”. Briggs et al., Neoplasia, 2012 Apr;14(4):297-310.
PCT Application # PCT/US2011/048635 published on May 18, 2012.