Journal
FRONTIERS IN PHARMACOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.852143
Keywords
HTS screening; fluorescence-based assay; immunomodulatory compounds; anti-cancer therapeutics; transcriptomics; CRISPR-Cas9
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This article introduces the importance of multi-omic approaches in cancer research, including phenotype-based high-throughput drug screening and computational approaches that link transcriptomic profiling with existing pharmaceutical compounds. In addition, it also discusses the application of CRISPR genome editing technology in studying drug resistance and sensitization mechanisms.
Multi-omic approaches offer an unprecedented overview of the development, plasticity, and resistance of cancer. However, the translation from anti-cancer compounds identified in vitro to clinically active drugs have a notoriously low success rate. Here, we review how technical advances in cell culture, robotics, computational biology, and development of reporter systems have transformed drug discovery, enabling screening approaches tailored to clinically relevant functional readouts (e.g., bypassing drug resistance). Illustrating with selected examples of success stories, we describe the process of phenotype-based high-throughput drug screening to target malignant cells or the immune system. Second, we describe computational approaches that link transcriptomic profiling of cancers with existing pharmaceutical compounds to accelerate drug repurposing. Finally, we review how CRISPR-based screening can be applied for the discovery of mechanisms of drug resistance and sensitization. Overall, we explore how the complementary strengths of each of these approaches allow them to transform the paradigm of pre-clinical drug development.
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