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Journal: Cell Reports Medicine
Article Title: Targeting of vulnerabilities of drug-tolerant persisters identified through functional genetics delays tumor relapse
doi: 10.1016/j.xcrm.2024.101471
Figure Lengend Snippet: Compound screen and CRISPR-based persister screen identified BRD2 as a vulnerability of DTEPs (A) Schematic representation of DTP induction and generation of DTEPs in PC9-SS cells. (B) Schematic of small-molecule screen on parental, senescent, DTP, and DTEP cells. (C) Top hits were selected based on the therapeutic window of senescent (Senes)/DTEP vs. parental. The x axis represents log fold change of the AUC score (Senes/DTEP vs. parental). The y axis represents the AUC score of Senes/DTEP cells. (D) CellTiter blue quantification of relevant viability of parental cells or DTEPs (osimertinib and gefitinib induced) treated with BET inhibitors. (E) Schematic of CRISPR-based kinome-wide genetic screen on DTEPs (n = 3 for each arm). (F) Top hits were selected based on the fold depletion of sgRNAs DTEP vs. parental. Genes with 4 sgRNA dropped out were identified as hits. (G) Western blot of BRD2 and β-actin in PC9-SS-iCas9 wild-type (WT) and BRD2 KO clones. (H) Relative fold change of persisters number based on cell counting obtained from WT and BRD2 KO clones after 14 days of osimertinib exposure. (I) IncuCyte-based proliferation of DTEPs of WT and BRD2 KO clones. Error bars in (D), (H), and (I) represent mean ± SD, n = 3 independent experiments. Statistical significance was calculated by 2-tailed Student’s t test (∗p ≤ 0.05; ∗∗p ≤ 0.01; ∗∗∗p ≤ 0.001).
Article Snippet:
Techniques: CRISPR, Western Blot, Clone Assay, Cell Counting
Journal: Cell Reports Medicine
Article Title: Targeting of vulnerabilities of drug-tolerant persisters identified through functional genetics delays tumor relapse
doi: 10.1016/j.xcrm.2024.101471
Figure Lengend Snippet:
Article Snippet:
Techniques: Recombinant, Membrane, cDNA Synthesis, Amplification, Mutagenesis, shRNA, Sequencing, Software
Journal: Cell reports
Article Title: Functional Genomics Identify Distinct and Overlapping Genes Mediating Resistance to Different Classes of Heterobifunctional Degraders of Oncoproteins
doi: 10.1016/j.celrep.2020.108532
Figure Lengend Snippet: KEY RESOURCES TABLE
Article Snippet:
Techniques: Recombinant, Staining, Cell Viability Assay, Cell Culture, Gel Extraction, Gene Expression, Control, CRISPR, Knock-Out, Activation Assay, Software
Journal: Journal of medicinal chemistry
Article Title: Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression
doi: 10.1021/acs.jmedchem.8b00506
Figure Lengend Snippet: Table 2.
Article Snippet: Antibodies for immunoblotting were
Techniques: Binding Assay, Recombinant