UNMET NEED
Chronic environmental exposure induces cancer stem cells (CSCs) with SOX2 overexpression, one of the most important CSC factor for urothelial cancer (UC). COX2 and YAP1 coordinately regulate SOX2 expression, and mutually compensate for the reduction of expression of SOX2 to maintain CSCs. Thus targeting the COX2/YAP/SOX2 signaling axis eliminates urothelial CSCs that enhance chemotherapeutic response.
TECHNICAL DESCRIPTION
JHU researchers elucidate molecular mechanisms of maintenance of CSCs population in UC. Their data showed that targeting the YAP1/COX2/SOX2 signaling axis eliminates cancer stem cells in urothelial carcinoma. They performed numerous in vitro and in vivo experiments to prove blocking of stem cell pathway by targeting YAP1 and COX2 increased chemotherapeutic sensitivity of urothelial cancer.
The invention demonstrates that urothelial stem cells have a survival selection advantage during carcinogen exposure, such as arsenic (As), and it facilitates their malignant transformation and in acquiring selective
phenotypes similar to CSC. They characterized As-induced CSCs using in vitro As-exposed HUC1 cell models and determined the feasibility of increasing therapeutic efficacy of chemotherapeutic drugs by combining with stem cell pathway inhibitors. Specifically, the present invention demonstrates treating subjects with cancer with a combination of COX2 and Yap1 inhibitors enhances CSC susceptibility to treatment such as chemotherapy and prolong patient survival.
MAJOR RESULTS
1. Chronic As exposure induces CSCs with SOX2 overexpression, one of the most important CSC factor for UC.
2. COX2 and YAP1 coordinately regulate SOX2 expression, and mutually compensate for the reduction of expression of SOX2 to maintain CSCs.
3. Targeting the COX2/YAP/SOX2 signaling axis eliminates urothelial CSCs.
DISEASE INDICATION
Urothelial Cancer
ASSOCIATED PUBLICATIONS
■ None at this time
TECHNOLOGY CLASSIFICATION
Primary Category: Therapeutics
Primary Subcategory:
ASSOCIATED REPORTS OF INVENTION (ROIs) AND INTELLECTUAL PROPERTY (IP) FILING NUMBERS
ROI # TITLE
C14031 PHARMACEUTICAL AGENTS TARGETING CANCER STEM CELLS
STATUS PRIORITY DATE IP FILING NUMBERS
US Provisional 3/7/2016 US 62/304,632
