Time-Based Switching Control of Genetic Regulatory Networks: Toward Sequential Drug Intake for Cancer Therapy.

ABSTRACT: As cancer growth and development typically involves multiple genes and pathways, combination therapy has been touted as the standard of care in the treatment of cancer. However, drug toxicity becomes a major concern whenever a patient takes 2 or more drugs simultaneously at the maximum tolerable dosage. A potential solution would be administering the drugs in a sequential or alternating manner rather than concurrently. This study therefore examines the feasibility of such an approach from a switched system control perspective. Particularly, we study how genetic regulatory systems respond to sequential (switched) drug inputs using the time-based switching mechanism. The design of the time-driven drug switching function guarantees the stability of the genetic regulatory system and the repression of the diseased genes. Simulation results using proof-of-concept models and the proliferation and survival pathways with sequential drug inputs show the effectiveness of the proposed approach.

SUBMITTER: Oduola WO 

PROVIDER: S-EPMC5431492 | biostudies-other | 2017

REPOSITORIES: biostudies-other