USE OF SMALL MOLECULE UNFOLDER PROTEIN RESPONSE MODULATORS TO TREAT TUMORS WITH ACTIVE SONIC HEDGEHOG (SSH) SIGNALING DUE TO SMOOTHENED (SMO) MUTATION

摘要

The present invention relates to methods for treating tumors having SMO mutations as well as diagnosing tumors with SMO mutations. The invention relates to methods for the treatment of cancer with ER stress-inducing compounds or UPR inducing compounds. The ER stress-inducing compounds or UPR inducing compounds might fill a clinical need for additional methods of targeting the Hh pathway, either in frontline combination therapy or in salvage therapy for relapsed patients who develop resistance to the available SMO inhibitor and offer a significant advantage over SMO-specific small molecules. Because ER stress modulators and UPR inducing compounds exploit a cellular process that is distinct from the Hh signaling pathway, their efficacy should be unaltered by acquired SMO mutation.