Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
1 Defining principles of combination drug mechanism of action 2 Introduction : Cancer and chemotherapy There are as many cancer-types as there are cancer-patients. Cancer development Inactivation of Tumor suppressor gene Onset of tumor development Activation of Oncogene Multiple targets for chemotherapy Combinatory chemotherapy - standard treatment Combinatorial effect are unknown 3 Objectives Exploring combination drug mechanism of action Meaning to define combination therapy statistically and experimentally, similar to single drug treatment. signature”-based prediction has provided a powerful new strategy for examining drug mechanism Understand why multy-drug treatment results in better outcome. 4 Overview of research inactivation • Infection of cells by shRNA 8 shRNA • Targeting checkpoint kinases or cell death regulator categorization • Exposure to chemotherapy regulation • Assessment of drug effect 5 Methods - Drug categories 6 Methods - Drug clustering Comparing drug signatures with the drug categories in our reference set. The initial drug category size in the reference set is defined Calculating negative control by adding drugs known to be in other cathegories to the equation. Gives fals linkage ratio. 7 Results - Mechanistic prediction Principal components analysis (PCA)- replotting drug combination behavior 8 In comparison to: 9 Discussion Using informatics tools to characterizes the genetic consequences of combining drug treatments combination mechanisms of action tend to represent weighted composites of single-drug classes. In some combinations, the mechanistic contribution of a singledrug component is negligible. Combination therapies act via the minimization of acquired resistance, the existence of cell-intrinsic drug synergy, or the maximization of the cumulative drug dose. Either drug A potentiates the mechanism of drug B or drug A plus drug B produces additive, yet distinguishable, effects. 10 Conclusion Combination therapy allow synergy or even neomorphic mechanism of action. Lower dosage of each of the drug components. Knowing the single- drug responses , “it will be possible to compute solutions that can minimize drug resistance over all variants of that population.” 11 Acknowledgment 12