Investigating Herpes Simplex Virus Type 1 and KB Oral Cancer Using Fractional Factorial Designs for Drug Combination Determination

• Activity Number: 507
• Type: Contributed
• Date/Time: Wednesday, August 6, 2014 : 10:30 AM to 12:20 PM
• Sponsor: Section on Physical and Engineering Sciences
• Author(s): Jessica Jaynes*+
• Keywords: Blocking ; Drug Combination ; Experimental Design ; Fractional Factorial Design

Abstract

Experimental design and analysis is an effective and commonly used tool in scientific investigations and industrial applications. For drug combination determination, many challenges and complexities arise when trying to understand a system with multiple drugs (e.g., three or more drugs) because the underlying biological system is intrinsically complex and there are potential multiple drug interactions. We propose a new class of composite designs based on a two-level factorial design and a three-level orthogonal array to investigate two biological systems: Herpes simplex virus type 1, with six antiviral drugs, and KB oral cancer, with 11 anti-cancer drugs. We show how the sequential use of two-level and three-level fractional factorial designs can screen for important drugs and drug interactions, as well as determine potential optimal drug dosages. By understanding the complex drug-drug interactions and drug-cell interactions, we identify optimal drug combinations with minimum additive dosages. These observations have practical implications in the understanding of antiviral, and anti-cancer drug mechanism that can result in better design of drug therapy.