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Global Translational Medicine

REVIEW ARTICLE
Challenges and advancements in high-

throughput screening strategies for cancer
therapeutics

2†
1†
3
1
Ruchi Roy *, Sunil Kumar Singh , Nashrah Ahmad , and Sweta Misra *
1 UICentre for Drug Discovery, College of Pharmacy, University of Illinois Chicago, Chicago, Illinois,
United States of America
2 Department of Surgery, University of Illinois Chicago, Illinois, United States of America
3 Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California,
United States of America

Abstract

Drug discovery relies on high-throughput screening (HTS) methods incorporating
both target- and cell-based assays. This comprehensive review delves into the
challenges and benefits associated with these assays within the context of HTS. The
strategies for developing screening assays, spanning both primary and secondary
screens for target identification, are discussed. Furthermore, we review the methods
of identifying the most efficacious drugs through these approaches for the treatment
† These authors contributed equally of cancer in detail. While various drugs have been identified for cancer treatment,
to this work. there remains a pressing need for more relevant phenotypic assays. These assays aim
*Corresponding authors: to produce the desired disease phenotype, with a specific emphasis on highlighting
Ruchi Roy targets rather than off-targets. The ultimate goal is to pave the way for innovative
(ruchiroy@uic.edu) drug development strategies that can effectively treat cancer patients, thereby
Sweta Misra
(sweta16@uic.edu) reducing the mortality rate.
Citation: Roy R, Singh SK,
Ahmad N, Misra S. Challenges and Keywords: Target-based screening; Phenotypic-based screening; Targets; Transcriptional
advancements in high-throughput
screening strategies for cancer reprogramming; High-throughput screening; Cancer therapeutics
therapeutics. Global Transl Med.
2024;3(1):2448.
https://doi.org/10.36922/gtm.2448
Received: December 15, 2023 1. Introduction
Accepted: January 10, 2024
Published Online: March 12, 2024 The current drug discovery paradigm is highly focused on high-throughput screening
Copyright: © 2024 Author(s). (HTS), through which large libraries of compounds are screened against the target of
This is an Open-Access article interest to identify suitable and most probable biological or pharmacological targets,
distributed under the terms of the aiming for beneficial therapeutic outcomes. The lead-identified targets are used as
1,2
Creative Commons Attribution
License, permitting distribution, probes to address biological questions in basic research.
and reproduction in any medium,
provided the original work is At present, combinatorial chemistry and genomics data are extensively employed in
properly cited. HTS within the drug discovery process. HTS often involves robotic systems for rapid
3
Publisher’s Note: AccScience testing of large compound libraries against a target or phenotype. It is important to
Publishing remains neutral with note the distinction between HTS and high-content screening, which emphasizes the
regard to jurisdictional claims in
published maps and institutional simultaneous analysis of multiple cellular features to provide more detailed information
affiliations. on compound effects but at a lower throughput. Target-based screening and phenotypic

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