Title :
Optimal Intervention in Markovian Gene Regulatory Networks With Random-Length Therapeutic Response to Antitumor Drug
Author :
Yousefi, Mohammadmahdi R. ; Datta, Amitava ; Dougherty, Edward
Author_Institution :
Dept. of Electr. & Comput. Eng., Ohio State Univ., Columbus, OH, USA
Abstract :
The most effective cancer treatments are the ones that prolong patients´ lives while offering a reasonable quality of life during and after treatment. The treatments must also carry out their actions rapidly and with high efficiency such that a very large percentage of tumor cells die or shift into a state where they stop proliferating. Due to biological and microenvironmental variabilities within tumor cells, the action period of an administered drug can vary among a population of patients. In this paper, based on a recently proposed model for tumor growth inhibition, we first probabilistically characterize the variability of the length of drug action. Then, we present a methodology to devise optimal intervention strategies for any Markovian genetic regulatory network governing the tumor when the antitumor drug has a random-length duration of action.
Keywords :
Markov processes; cancer; cellular biophysics; drugs; genetics; patient treatment; probability; tumours; Markovian genetic regulatory network; antitumor drug; biological variability; cancer treatment; microenvironmental variability; optimal intervention; random-length therapeutic response; tumor cells; tumor growth inhibition; Biological system modeling; Drugs; Mathematical model; Probability distribution; Sociology; Statistics; Tumors; Cancer therapy; gene regulatory networks (GRNs); optimal intervention; probabilistic Boolean networks (PBNs); tumor growth inhibition (TGI) model;
Journal_Title :
Biomedical Engineering, IEEE Transactions on
DOI :
10.1109/TBME.2013.2272891