Genome-wide synthetic lethal CRISPR screen identifies FIS1 as a genetic interactor of ALS-linked C9ORF72
Sign Up to like & getrecommendations! Published in 2020 at "Brain Research"
DOI: 10.1016/j.brainres.2019.146601
Abstract: Mutations in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis (ALS). Both toxic gain of function and loss of function pathogenic mechanisms have been proposed. Accruing evidence from mouse knockout studies… read more here.
Keywords: genome wide; c9orf72; wide synthetic; lethal crispr ... See more keywords
Gene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras
Sign Up to like & getrecommendations! Published in 2017 at "Cell"
DOI: 10.1016/j.cell.2017.01.013
Abstract: The genetic dependencies of human cancers widely vary. Here, we catalog this heterogeneity and use it to identify functional gene interactions and genotype-dependent liabilities in cancer. By using genome-wide CRISPR-based screens, we generate a gene… read more here.
Keywords: gene essentiality; gene networks; oncogenic ras; gene ... See more keywords
Synthetic Lethal Interaction of SHOC2 Depletion with MEK Inhibition in RAS-Driven Cancers.
Sign Up to like & getrecommendations! Published in 2019 at "Cell reports"
DOI: 10.1016/j.celrep.2019.08.090
Abstract: The mitogen-activated protein kinase (MAPK) pathway is a critical effector of oncogenic RAS signaling, and MAPK pathway inhibition may be an effective combination treatment strategy. We performed genome-scale loss-of-function CRISPR-Cas9 screens in the presence of… read more here.
Keywords: mek inhibition; inhibition; depletion; ras driven ... See more keywords
Synthetic Lethal Interaction between the ESCRT Paralog Enzymes VPS4A and VPS4B in Cancers Harboring Loss of Chromosome 18q or 16q
Sign Up to like & getrecommendations! Published in 2021 at "Cell reports"
DOI: 10.1016/j.celrep.2021.109367
Abstract: Jasper E. Neggers, Brenton R. Paolella, Adhana Asfaw, Michael V. Rothberg, Thomas A. Skipper, Annan Yang, Radha L. Kalekar, John M. Krill-Burger, Neekesh V. Dharia, Guillaume Kugener, Jérémie Kalfon, Chen Yuan, Nancy Dumont, Alfredo Gonzalez,… read more here.
Keywords: interaction escrt; enzymes vps4a; lethal interaction; paralog enzymes ... See more keywords
A synthetic lethal bullet
Sign Up to like & getrecommendations! Published in 2017 at "Nature Nanotechnology"
DOI: 10.1038/s41565-017-0038-2
Abstract: Nanoparticles loaded with paclitaxel and nintedanib induce synthetic lethality in endometrial cancer cells. read more here.
Keywords: lethal bullet; synthetic lethal;
WRN Helicase is a Synthetic Lethal Target in Microsatellite Unstable Cancers
Sign Up to like & getrecommendations! Published in 2019 at "Nature"
DOI: 10.1038/s41586-019-1102-x
Abstract: Synthetic lethality—an interaction between two genetic events through which the co-occurrence of these two genetic events leads to cell death, but each event alone does not—can be exploited for cancer therapeutics1. DNA repair processes represent… read more here.
Keywords: dna; target; helicase; synthetic lethal ... See more keywords
A high-throughput screen to identify novel synthetic lethal compounds for the treatment of E-cadherin-deficient cells
Sign Up to like & getrecommendations! Published in 2019 at "Scientific Reports"
DOI: 10.1038/s41598-019-48929-0
Abstract: The cell-cell adhesion protein E-cadherin (CDH1) is a tumor suppressor that is required to maintain cell adhesion, cell polarity and cell survival signalling. Somatic mutations in CDH1 are common in diffuse gastric cancer (DGC) and… read more here.
Keywords: lethal compounds; novel synthetic; treatment; cell ... See more keywords
VRK1 Is a Synthetic–Lethal Target in VRK2-Deficient Glioblastoma
Sign Up to like & getrecommendations! Published in 2022 at "Cancer Research"
DOI: 10.1158/0008-5472.can-21-4443
Abstract: A paralog synthetic–lethal interaction between VRK1 and VRK2 sensitizes VRK2-methylated glioblastoma to perturbation of VRK1 kinase activity, supporting VRK1 as a drug discovery target in this disease. read more here.
Keywords: synthetic lethal; glioblastoma; lethal target; vrk1 synthetic ... See more keywords
Synthetic Lethal Screens Reveal Cotargeting FAK and MEK as a Multimodal Precision Therapy for GNAQ-Driven Uveal Melanoma
Sign Up to like & getrecommendations! Published in 2021 at "Clinical Cancer Research"
DOI: 10.1158/1078-0432.ccr-20-3363
Abstract: Purpose: Uveal melanoma is the most common eye cancer in adults. Approximately 50% of patients with uveal melanoma develop metastatic uveal melanoma (mUM) in the liver, even after successful treatment of the primary lesions. mUM… read more here.
Keywords: uveal melanoma; mek; synthetic lethal; fak ... See more keywords
Abstract B177: Synthetic lethal approach identifies potent and selective TTK and CLK inhibitor with preclinical anticancer activity in triple-negative breast cancer model
Sign Up to like & getrecommendations! Published in 2018 at "Molecular Cancer Therapeutics"
DOI: 10.1158/1535-7163.targ-17-b177
Abstract: Historically, synthetic lethal-based drug discovery has yielded a high percentage of novel, first-in-class drugs while uncovering new tumor biology. Using a synthetic lethal approach, we identified one compound that preferentially induced apoptosis in triple-negative breast… read more here.
Keywords: ttk; breast cancer; approach; cancer ... See more keywords
Abstract C018: Primary tumor data analysis reveals novel synthetic lethal dependencies between KRAS mutation and the spliceosome
Sign Up to like & getrecommendations! Published in 2019 at "Molecular Cancer Therapeutics"
DOI: 10.1158/1535-7163.targ-19-c018
Abstract: Identification of mutation-specific targeted therapies is a critical challenge in precision medicine. Synthetic lethality provides the basis for an approach to identify new therapeutic targets for mutations that are difficult to target directly, since in… read more here.
Keywords: tumor; primary tumor; kras mutant; cancer ... See more keywords