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Global Translational Medicine Role of HTS in cancer therapeutics

screening represent different approaches to HTS, each However, testing the large compound libraries for
with its advantages and challenges. These approaches their binding affinity or biological activity with the aim of
are selected based on the specific goals of the research, generating a sufficient number of hits for a drug is a very
4,5
the stage of drug discovery, and the available knowledge costly process. Recent studies are leaning towards favoring
about the disease and potential drug targets. Target- an information-driven strategy over screening a vast
based screening focuses on identifying compounds that number of compounds, aiming to enhance the probability
interact with a specific molecular target, such as a protein of success. The complexity and cost escalate as we strive to
or enzyme associated with a disease whereas phenotypic replicate more relevant disease phenotypes. This emphasizes
screening involves testing compounds based on their the need for methods that foster an integrated approach
ability to induce a desired cellular phenotype without to enhance quantity, quality, and cost efficiency. The
prior knowledge of the target. Target-based screening is application of combinatorial chemistry involves screening
commonly used in the early stages of drug discovery to a diverse array of compounds in one comprehensive
identify lead compounds. This approach typically employs sweep, facilitating rapid concurrent screening against
assays involving purified targets, using techniques like specific drug targets. However, the effectiveness of these
fluorescence resonance energy transfer (FRET) or surface smart libraries in drug discovery relies heavily on precise
plasmon resonance (SPR). Phenotypic screening is often knowledge of the druggable target. Genomics plays a
applied later in drug discovery, especially when the crucial role in this context, providing insights into the type
molecular basis of a disease is unclear. It utilizes cellular or of mutation and its burden, which varies depending on the
organismal models and may involve high-content imaging disease and age. For instance, an integrated application
systems, automated microscopy, and other techniques of genomic, in vitro, and in vivo tests was adopted in a
for analyzing complex phenotypes (summarized in case study on a 10-year-old boy with multiple recurrent
Table 1 and Figure 1). glioblastoma facing challenges in treatment due to inter

Figure 1. Overview of the drug selection process in high-throughput screening and the workflow of selecting an effective drug.

Volume 3 Issue 1 (2024) 2 https://doi.org/10.36922/gtm.2448