Cancer Therapy Design Based on Pathway Information

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ABSTRACTObjective: The main objective of this project is to develop a more systematic approach towards cancer treatment in order to a better success rate. Current cancer therapies suffer from two main drawbacks: (i) they do not take into account the genetic differences that exist between any two individuals, even if they are perfectly healthy; and (ii) they fail to pinpoint the precise malfunctioning in the cellular signaling that has led to the cancer seen in a particular patient. Intellectual Merit: The number of cells in a multi-cellular organism such as a human being is under very tight control and, under normal circumstances, there is some kind of a balance between new cell production and cell death. Roughly speaking, cancer results when there is excessive cell division or reduced cell death due to some malfunctioning in the cell number control system. What makes cancer therapy so difficult is that this malfunctioning can happen in many different ways and at many different locations. This project seeks to use prior information from the biological literature to model the normal cell signaling network as a digital circuit, whose output upon a possible breakdown can be used to pinpoint the precise breakdown location and accordingly tailor the therapy. The theoretical work will be experimentally validated. Broader Impacts: Since the research in this project specifically targets cancer therapy, its potential societal benefits in terms of ultimately saving human lives could be enormous. In addition, the methods developed here have the potential to impact other areas such as toxicological studies focusing on cellular response to different stresses. Every effort will be made to ensure that the benefits of the project reach a wide audience, including minorities and domestic students. In addition, the results of this project will lead to the publication of a new book.