7af3058622667b1a62814970f031943d cancers_a2021v13n7p1591.pdf 8946d25c1197a1230db967e647994bc0a7425804 cancers_a2021v13n7p1591.pdf f8320cecdacb577a0d263db4ceeaad7e2b5e08b7ae6f873eb0dddc9f0de39422 cancers_a2021v13n7p1591.pdf Title: CRISPR Screens in Synthetic Lethality and Combinatorial Therapies for Cancer Subject: 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. Keywords: CRISPR screen; synthetic lethality; combinatorial therapy; cancer therapeutic resistance Author: Laia Castells-Roca, Eudald Tejero, Benjamín Rodríguez-Santiago and Jordi Surrallés Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Apr 6 11:33:51 2021 CEST ModDate: Fri Apr 9 05:15:38 2021 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 22 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1023940 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- HCRKXL+VnURWPalladioL Type 1 Custom yes yes no 10 0 MNLCIY+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 OGJTYU+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 EIOKHJ+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 YSPQJI+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 37 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 59 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 63 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 67 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 87 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 91 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 95 0 SAUAIP+CMSY10 Type 1 Builtin yes yes no 103 0 WNOXSG+Arial-BoldMT TrueType MacRoman yes yes no 122 0 GQNEPP+Calibri-Bold TrueType WinAnsi yes yes yes 125 0 DMISED+Calibri TrueType WinAnsi yes yes yes 129 0 VHQEYN+Calibri-BoldItalic TrueType WinAnsi yes yes yes 133 0 VHYHSI+Calibri-Italic TrueType WinAnsi yes yes yes 137 0 FENMUV+TimesNewRomanPS-BoldItalicMT TrueType MacRoman yes yes no 141 0 CBSRZX+EURM10 Type 1 Builtin yes yes no 371 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:51:49 CEST RepresentationInformation: cancers_a2021v13n7p1591.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 11:50:52 CEST Size: 1023940 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 845 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: CRISPR/Cas9 Screens Steps Destination: section.2 Children: Item: Title: CRISPR Library Destination: subsection.2.1 Item: Title: Considerations for Screening in Cancer Cell Lines Destination: subsection.2.2 Item: Title: Setting Up the Experimental Protocol Destination: subsection.2.3 Item: Title: CRISPR Screen Destination: subsection.2.4 Item: Title: Screen Analysis Destination: subsection.2.5 Item: Title: Candidate Hits Validation Destination: subsection.2.6 Item: Title: CRISPR/Cas Screens in Cancer Destination: section.3 Children: Item: Title: Synthetic Lethal Screens Destination: subsection.3.1 Item: Title: Synthetic Viable Screens Destination: subsection.3.2 Item: Title: Novel Drug Targets Screens Destination: subsection.3.3 Item: Title: Pooled CRISPR Screens Based on FACS Destination: subsection.3.4 Item: Title: 3D Cultured Cancer Models CRISPR Screens Destination: subsection.3.5 Item: Title: Ex Vivo and In Vivo CRISPR Screens Destination: subsection.3.6 Item: Title: Non-Coding Gene Targets CRISPR Screens Destination: subsection.3.7 Item: Title: Future Perspectives Destination: section.4 Item: Title: References Destination: section.4 Info: Title: CRISPR Screens in Synthetic Lethality and Combinatorial Therapies for Cancer Author: Laia Castells-Roca, Eudald Tejero, Benjamín Rodríguez-Santiago and Jordi Surrallés Subject: 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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