Integrating Phenotypic Search and Phosphoproteomic Profiling of Active Kinases for Optimization of Drug Mixtures for RCC Treatment.

ABSTRACT: Combined application of multiple therapeutic agents presents the possibility of enhanced efficacy and reduced development of resistance. Definition of the most appropriate combination for any given disease phenotype is challenged by the vast number of theoretically possible combinations of drugs and doses, making extensive empirical testing a virtually impossible task. We have used the streamlined-feedback system control (s-FSC) technique, a phenotypic approach, which converges to optimized drug combinations (ODC) within a few experimental steps. Phosphoproteomics analysis coupled to kinase activity analysis using the novel INKA (integrative inferred kinase activity) pipeline was performed to evaluate ODC mechanisms in a panel of renal cell carcinoma (RCC) cell lines. We identified differe

SUBMITTER: van Beijnum JR 

PROVIDER: S-EPMC7564658 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature