Cargando…

Recent Advances in Cancer Drug Discovery Through the Use of Phenotypic Reporter Systems, Connectivity Mapping, and Pooled CRISPR Screening

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 cultu...

Descripción completa

Detalles Bibliográficos
Autores principales: Salame, Natasha, Fooks, Katharine, El-Hachem, Nehme, Bikorimana, Jean-Pierre, Mercier, François E., Rafei, Moutih
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250974/
https://www.ncbi.nlm.nih.gov/pubmed/35795568
http://dx.doi.org/10.3389/fphar.2022.852143
_version_ 1784739931642396672
author Salame, Natasha
Fooks, Katharine
El-Hachem, Nehme
Bikorimana, Jean-Pierre
Mercier, François E.
Rafei, Moutih
author_facet Salame, Natasha
Fooks, Katharine
El-Hachem, Nehme
Bikorimana, Jean-Pierre
Mercier, François E.
Rafei, Moutih
author_sort Salame, Natasha
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9250974
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-92509742022-07-05 Recent Advances in Cancer Drug Discovery Through the Use of Phenotypic Reporter Systems, Connectivity Mapping, and Pooled CRISPR Screening Salame, Natasha Fooks, Katharine El-Hachem, Nehme Bikorimana, Jean-Pierre Mercier, François E. Rafei, Moutih Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2022-06-20 /pmc/articles/PMC9250974/ /pubmed/35795568 http://dx.doi.org/10.3389/fphar.2022.852143 Text en Copyright © 2022 Salame, Fooks, El-Hachem, Bikorimana, Mercier and Rafei. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Salame, Natasha
Fooks, Katharine
El-Hachem, Nehme
Bikorimana, Jean-Pierre
Mercier, François E.
Rafei, Moutih
Recent Advances in Cancer Drug Discovery Through the Use of Phenotypic Reporter Systems, Connectivity Mapping, and Pooled CRISPR Screening
title Recent Advances in Cancer Drug Discovery Through the Use of Phenotypic Reporter Systems, Connectivity Mapping, and Pooled CRISPR Screening
title_full Recent Advances in Cancer Drug Discovery Through the Use of Phenotypic Reporter Systems, Connectivity Mapping, and Pooled CRISPR Screening
title_fullStr Recent Advances in Cancer Drug Discovery Through the Use of Phenotypic Reporter Systems, Connectivity Mapping, and Pooled CRISPR Screening
title_full_unstemmed Recent Advances in Cancer Drug Discovery Through the Use of Phenotypic Reporter Systems, Connectivity Mapping, and Pooled CRISPR Screening
title_short Recent Advances in Cancer Drug Discovery Through the Use of Phenotypic Reporter Systems, Connectivity Mapping, and Pooled CRISPR Screening
title_sort recent advances in cancer drug discovery through the use of phenotypic reporter systems, connectivity mapping, and pooled crispr screening
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250974/
https://www.ncbi.nlm.nih.gov/pubmed/35795568
http://dx.doi.org/10.3389/fphar.2022.852143
work_keys_str_mv AT salamenatasha recentadvancesincancerdrugdiscoverythroughtheuseofphenotypicreportersystemsconnectivitymappingandpooledcrisprscreening
AT fookskatharine recentadvancesincancerdrugdiscoverythroughtheuseofphenotypicreportersystemsconnectivitymappingandpooledcrisprscreening
AT elhachemnehme recentadvancesincancerdrugdiscoverythroughtheuseofphenotypicreportersystemsconnectivitymappingandpooledcrisprscreening
AT bikorimanajeanpierre recentadvancesincancerdrugdiscoverythroughtheuseofphenotypicreportersystemsconnectivitymappingandpooledcrisprscreening
AT mercierfrancoise recentadvancesincancerdrugdiscoverythroughtheuseofphenotypicreportersystemsconnectivitymappingandpooledcrisprscreening
AT rafeimoutih recentadvancesincancerdrugdiscoverythroughtheuseofphenotypicreportersystemsconnectivitymappingandpooledcrisprscreening