A new approach to assess drug sensitivity in cells for novel drug discovery

ABSTRACT

Introduction: There is a pressing need to improve strategies to select candidate drugs early on in the drug development pipeline, especially in oncology, as the efficiency of new drug approval has steadily declined these past years. Traditional methods of drug screening have relied on low-cost assays on cancer cell lines growing on plastic dishes. Recent massive-scale screens have generated big data amenable for sophisticated computational modeling and integration with clinical data. However, 2D culturing has several intrinsic limitations and novel methodologies have been devised for culturing in three dimensions, to include cells from the tumor immune microenvironment. These major improvements are bringing in vitro systems even closer to a physiological, more clinically relevant state.

Areas covered: In this article, the authors review the literature on methodologies for early-phase drug screening, focusing on in vitro systems and analyzing both novel experimental and statistical approaches. The article does not cover the expanding literature on in vivo systems.

Expert opinion: The popularity of three-dimensional systems is exploding, driven by the development of ‘organoid’ derivation technology in 2009. These assays are growing in sophistication to accommodate the increasing need by modern oncology to develop drugs that target the microenvironment

KEYWORDS:

• Drug discovery
• cell lines
• organoids
• multicellular co-cultures

Article highlights

• Recent high-throughput screens have pushed the boundaries of conventional 2D cancer cell line culturing to its limit

• Conventional 2D screens have inherent biological and methodological limitations

• Organoids and other 3D co-culturing may represent widely applicable technology for improved screens

• Higher clinical relevance of 3D co-culturing is likely but has to be demonstrated directly

• Coculturing organoids with immune cells may allow personalized large-scale immune checkpoint inhibitor screens

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This manuscript has not been funded.