Combination therapy design for cancer: A digital systems approach

摘要

Cancer encompasses various diseases associated with loss of cell-cycle control, leading to uncontrolled cell proliferation and/or reduced apoptosis. Cancer is usually caused by malfunction(s) in the cellular signaling pathways. Malfunctions occur in different ways and at different locations in a pathway. Consequently, therapy design should first identify the location and type of malfunction and then arrive at a suitable drug combination. We consider the growth factor (GF) signaling pathways, widely studied in the context of cancer. Interactions between different pathway components are modeled using Boolean logic gates. All possible single malfunctions in the resulting circuit are enumerated and responses of the different malfunctioning circuits to a ‘test’ input are used to group the malfunctions into classes. Effects of different drugs, targeting different parts of the Boolean circuit, are taken into account in deciding drug efficacy, thereby mapping each malfunction to an appropriate set of drugs.