Targeting stem cell populations in lung cancer by modulating the Wnt and p53 path

DESCRIPTION (provided by applicant): Despite significant advancements in modern medicine with regards to surgery, radiation therapy and imaging of tumors, the survival rate for patients with non-small-cell lung carcinoma (NSCLC) remain almost identical to20 years ago. Current therapies targeting the proliferative mechanisms of NSCLC cancers such as K-RAS and EGFR have been the focus of a large effort in the pharmaceutical industry and academic laboratories. Such therapies have benefits over classical chemotherapy agents in prolonging median progression-free survival but have almost no effect on overall survival. In recent years, it has become clear that cancers are highly heterogeneous and the initial sensitivity to chemotherapy is the effect on the more differentiated (highly proliferative) cell types. The cancer stem cell population distributed within the initial tumor mass is resistant to chemotherapy and displays a highly invasive/metastatic phenotype. StemSynergy Therapeutics Inc. (SSTI) is a biopharmaceutical company focused on the discovery, development, and commercialization of drugs that target pathways fundamental to stem cells and cancer stem cells. Recent high profile literature studies have shown that cancer stem cell populations in NSCLC demonstrate aberrant Wnt pathway activity are sensitive to secreted Wnt inhibitors. There is an urgent need for inhibitors of the Wnt pathway because currently, there are no FDA-approved drugs or drugs in late-stage clinical trials that target this pathway. This application describes the discovery and development of a new class of Wnt pathway inhibitors that activate Casein Kinase 1a (CK1a). Additional to the highly potent Wnt inhibitory activity, these small molecules activate p53. StemSynergy aims to develop atreatment for NSCLC that synergizes with current FDA approved drugs for NSCLC by targeting the drug resistant cells/cancer stem cells to eliminate ALL cancer cells and therefore increase survival for lung cancer patients. PUBLIC HEALTH RELEVANCE:Lung cancer is the largest cause of mortality and morbidity with 1.4 million deaths per year worldwide. StemStynergy is developing Wnt inhibitors to target the drug resistant cancer stem cell population to decrease metastasis and increase overall survival.