ACCELERATING ANTI_CANCER THERAPEUTIC STRATEGIES BY USING CUTTING EDGE CELL-BASED HIGH_THROUGHPUT ASSAYS - ISBE 2015 Conference

Moshe Elkabets ^1,2 Qing Cheng ³ Alan Huang ³ Samual Brook ² Maurizion Scaltriti ² Jose Baselga ²

¹Immunology Microbiology and Genetics, Ben-Gurion University of the Negev, Beer-Sheva
²Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York
³Oncology Translational Medicine, Novartis Institutes, Cambridge

Drug resistance is a major problem in the treatment of cancer patients. Identifying the molecular mechanisms by which tumors acquire resistance to targeted therapy is important to improve the effectiveness of treatment by inducing tumor shrinkage and/or prolonging the duration of clinical responses. The recent development of unbiased cell-based high-throughput methodologies such as shRNA re-sensitization and rescue-secretome screens provide opportunities to gain a comprehensive snapshot of the potential mechanisms of drug resistance. Furthermore, expression profiling of proteins using CEER or RPPA technology and analysis of gene expression using RNAseq are commonly used to characterize the changes that occur in cells during transient or chronic exposure to the drug. Using these technologies, we have been able to identify that reactivation of mTOR is a mechanism of resistance to PI3Ka inhibitors in PIK3CA amplified and mutated breast, esophageal and head and neck cancers. Overall, the development of novel technologies is crucial in accelerating cancer therapy.