Design of experiment approach to leukemia studies

Abstract

Cancer remains a leading cause of death worldwide, accounting for 7.9 million deaths in 2007, and is projected to rise to an estimated 12 million deaths in year 2030. To date, an extensive amount of work has been done to characterize the therapeutic effects and toxicity of anti-cancer compounds as well as the effects of cytokines on the expansion of HSC. However, conventional approaches often employ a dose-response method which neglects to consider interactive effects. In addition, there is a lack of use of a statistically optimized experimental design in current biological practices and cell culture studies.

This study is conducted with the aim of improving the quality and efficiency of cancer studies by evaluating the feasibility of utilizing DOE in Leukemia Therapy. Two examples are used in this study, one for the characterization of anti-cancer drug and the other in optimizing stem cell cultures for expanding HSC cell populations; both of which are therapeutic approaches to leukemia therapy.

The case studies conducted produced consistent findings on the DOE approach which revealed improvement in efficiency (reduced number of experimental runs), maximization of knowledge (interactive effects, differentiate antagonistic/synergistic interactions, quantitative models, prediction of parameters at region of interest) and the providence of statistical confidence (error analysis over entire process region to draw objective conclusions), which serve to highlight the viability of DOE as a feasible alternative to the OFAT approach as a characterization method for enhancing the quality of cancer studies.