The Impact of Cellular Environment on In Vitro Drug Screening

Abstract

There are various reasons for drug failure in the developmental stage including toxicity, adverse effects and inefficacy. This is likely due to the differences in drug behavior between a simple and controlled cell culture system to that of a more complex whole organism environment. While the use of human phenotypical cells relevant to the condition may provide more accurate screening results, they are susceptible to producing false positives as cells are continuously influenced by constant chemical and physical interaction with the surrounding microenvironment. Therefore, several microenvironmental and pharmacomechanical aspects must be factored in during tissue culture drug screening.

Plain Language Summary

Drug discovery is a lengthy process that goes through several preclinical and clinical testing stages. One of the earliest stages in preclinical testing involves testing new drug using isolated cells. This system is an important tool in research and a commonly used technique in drug testing. However, a number of subtle, but important issues appear to affect its results. Therefore, in this review, we attempt to address some of the important issues that could lead to false positive or negative hits.

Keywords:

• cell culture
• drug screening
• microenvironment
• oxidative tension
• pH
• ROS

Author contributions

A Moldasheva drafted the manuscript and prepared the figures; L Bakhyt and D Bulanin were involved in data collection and manuscript preparation; and M Aljofanwas involved in study conception, design and manuscript preparation. All authors reviewed the results and approved the final version of the manuscript.

Acknowledgments

D Bulanin is supported by a grant awarded by the Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan (grant no. AP14872052).

Financial & competing interests disclosure

The publication was supported by the Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan (grant no. AP14872052). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.