CRISPR Screens in Synthetic Lethality and Combinatorial Therapies for Cancer

Cancer is a complex disease resulting from the accumulation of genetic dysfunctions. Tumor heterogeneity causes the molecular variety that divergently controls responses to chemotherapy, leading to the recurrent problem of cancer reappearance. For many decades, efforts have focused on identifying es...

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Main Authors: Laia Castells-Roca, Eudald Tejero, Benjamín Rodríguez-Santiago, Jordi Surrallés
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/7/1591
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author Laia Castells-Roca
Eudald Tejero
Benjamín Rodríguez-Santiago
Jordi Surrallés
author_facet Laia Castells-Roca
Eudald Tejero
Benjamín Rodríguez-Santiago
Jordi Surrallés
author_sort Laia Castells-Roca
collection DOAJ
description Cancer is a complex disease resulting from the accumulation of genetic dysfunctions. Tumor heterogeneity causes the molecular variety that divergently controls responses to chemotherapy, leading to the recurrent problem of cancer reappearance. For many decades, efforts have focused on identifying essential tumoral genes and cancer driver mutations. More recently, prompted by the clinical success of the synthetic lethality (SL)-based therapy of the PARP inhibitors in homologous recombinant deficient tumors, scientists have centered their novel research on SL interactions (SLI). The state of the art to find new genetic interactions are currently large-scale forward genetic CRISPR screens. CRISPR technology has rapidly evolved to be a common tool in the vast majority of laboratories, as tools to implement CRISPR screen protocols are available to all researchers. Taking advantage of SLI, combinatorial therapies have become the ultimate model to treat cancer with lower toxicity, and therefore better efficiency. This review explores the CRISPR screen methodology, integrates the up-to-date published findings on CRISPR screens in the cancer field and proposes future directions to uncover cancer regulation and individual responses to chemotherapy.
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spelling doaj.art-eecb18fe119b4492a04e8ae2e30a205a2023-11-21T13:23:54ZengMDPI AGCancers2072-66942021-03-01137159110.3390/cancers13071591CRISPR Screens in Synthetic Lethality and Combinatorial Therapies for CancerLaia Castells-Roca0Eudald Tejero1Benjamín Rodríguez-Santiago2Jordi Surrallés3Genome Instability and DNA Repair Syndromes Group, Sant Pau Biomedical Research Institute (IIB Sant Pau) and Join Unit UAB-IR Sant Pau on Genomic Medicine, 08041 Barcelona, SpainSant Pau Biomedical Research Institute (IIB Sant Pau), 08041 Barcelona, SpainGenetics Department, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, SpainGenome Instability and DNA Repair Syndromes Group, Sant Pau Biomedical Research Institute (IIB Sant Pau) and Join Unit UAB-IR Sant Pau on Genomic Medicine, 08041 Barcelona, SpainCancer is a complex disease resulting from the accumulation of genetic dysfunctions. Tumor heterogeneity causes the molecular variety that divergently controls responses to chemotherapy, leading to the recurrent problem of cancer reappearance. For many decades, efforts have focused on identifying essential tumoral genes and cancer driver mutations. More recently, prompted by the clinical success of the synthetic lethality (SL)-based therapy of the PARP inhibitors in homologous recombinant deficient tumors, scientists have centered their novel research on SL interactions (SLI). The state of the art to find new genetic interactions are currently large-scale forward genetic CRISPR screens. CRISPR technology has rapidly evolved to be a common tool in the vast majority of laboratories, as tools to implement CRISPR screen protocols are available to all researchers. Taking advantage of SLI, combinatorial therapies have become the ultimate model to treat cancer with lower toxicity, and therefore better efficiency. This review explores the CRISPR screen methodology, integrates the up-to-date published findings on CRISPR screens in the cancer field and proposes future directions to uncover cancer regulation and individual responses to chemotherapy.https://www.mdpi.com/2072-6694/13/7/1591CRISPR screensynthetic lethalitycombinatorial therapycancer therapeutic resistance
spellingShingle Laia Castells-Roca
Eudald Tejero
Benjamín Rodríguez-Santiago
Jordi Surrallés
CRISPR Screens in Synthetic Lethality and Combinatorial Therapies for Cancer
Cancers
CRISPR screen
synthetic lethality
combinatorial therapy
cancer therapeutic resistance
title CRISPR Screens in Synthetic Lethality and Combinatorial Therapies for Cancer
title_full CRISPR Screens in Synthetic Lethality and Combinatorial Therapies for Cancer
title_fullStr CRISPR Screens in Synthetic Lethality and Combinatorial Therapies for Cancer
title_full_unstemmed CRISPR Screens in Synthetic Lethality and Combinatorial Therapies for Cancer
title_short CRISPR Screens in Synthetic Lethality and Combinatorial Therapies for Cancer
title_sort crispr screens in synthetic lethality and combinatorial therapies for cancer
topic CRISPR screen
synthetic lethality
combinatorial therapy
cancer therapeutic resistance
url https://www.mdpi.com/2072-6694/13/7/1591
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