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Defeat mutant KRAS with synthetic lethality
2016
Small GTPases
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An alternative indirect approach by targeting synthetic lethal interactors of mutant RAS is underway. ...
In this commentary, we will summarize the state-of-the art for the direction of synthetic lethality, and also speculate on the future development of this approach. ...
approach to directly identify drugs that target the essential signaling for the growth of KRAS-mutant tumors. ...
doi:10.1080/21541248.2016.1213783
pmid:27463838
pmcid:PMC5680709
fatcat:3d45mc7yb5ckpedz2szq7vld7q
RNAi-Induced synthetic lethality in cancer therapy
2009
Cancer Biology & Therapy
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Hackett for the scientific edit. ...
. 10 This concept now has been widely exploited to identify gene targets for cancer therapy. ...
14 In this issue of Cancer Biology & Therapy, Michiue et al. ...
doi:10.4161/cbt.8.23.10539
pmid:19949302
pmcid:PMC4512945
fatcat:yiakrc3wjrb2vku4udcyrnuvri
COBRA methods and metabolic drug targets in cancer
2017
Molecular & Cellular Oncology
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The identification of therapeutic strategies exploiting the metabolic alterations of malignant cells is a relevant area in cancer research. ...
Here, we discuss a novel computational method, based on the COBRA (COnstraint-Based Reconstruction and Analysis) framework for metabolic networks, to perform this task. ...
The COBRA approach is considered promising to elucidate novel drug targets in cancer. ...
doi:10.1080/23723556.2017.1389672
pmid:29404389
fatcat:owjo4x5sjnd7xgi4jyiclxxh5y
Approaches to identifying synthetic lethal interactions in cancer
2015
The Yale Journal of Biology and Medicine
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Targeting synthetic lethal interactions is a promising new therapeutic approach to exploit specific changes that occur within cancer cells. ...
Genome-wide computational approaches, such as DAISY, also have been successful in predicting synthetic lethal interactions from both cancer cell lines and patient samples. ...
In identifying genes that are synthetically lethal within each cancer type, we gain an understanding of the molecular biology of those cancers and how it can be specifically exploited. ...
pmid:26029013
pmcid:PMC4445436
fatcat:76yb4m7ffjbtpmz4kiefhrvekq
Dissecting Cancer Pathways and Vulnerabilities with RNAi
2005
Cold Spring Harbor Symposia on Quantitative Biology
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However, functional annotation exists for only a small proportion of genes in the human genome, raising the likelihood that many cancer-relevant genes and potential drug targets await identification. ...
However, such approaches in mammalian cells have been limited by the lack of genetic tools. ...
The synthetic lethal approach has not been exploited in the past because there were no robust methods for systematically identifying synthetic lethal genes. ...
doi:10.1101/sqb.2005.70.031
pmid:16869781
fatcat:twspiofqjbdtzdarrnqtqshkqa
Using Functional Genetics to Understand Breast Cancer Biology
2010
Cold Spring Harbor Perspectives in Biology
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In this article, we describe how functional genetic studies can help us understand the biology of breast cancer, how it can be used to identify novel targets for breast cancer therapy, and how it can help ...
The discovery in 2001 that gene silencing through RNA interference (RNAi) can also be brought about in mammalian cells paved the way for large scale loss-of-function genetic screens in higher organisms ...
The second approach to identifying targets synthetically lethal with a K-RAS mutation was the use of a genome wide pooled approach targeting about 12,000 genes in a matched pair of isogenic K-RAS mutant ...
doi:10.1101/cshperspect.a003327
pmid:20519343
pmcid:PMC2890198
fatcat:j3nmdhmob5eqfngu7cajdsgcnq
Synthetic Vulnerabilities in the KRAS Pathway
2022
Cancers
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One potential approach is the identification of KRAS-specific synthetic lethal vulnerabilities. ...
synthetic lethal interactions with a promising future as potential clinical treatments in KRAS-mutant cancers. ...
Screening Approaches to Identify Synthetic Lethal Interactions with KRAS The two main genetic approaches to identifying synthetic lethal targets in human cancer cells are loss-of-function screens based ...
doi:10.3390/cancers14122837
pmid:35740503
pmcid:PMC9221492
fatcat:mdxwafvzizcvfioxzx66lr4r5q
Desperately Seeking Genotype-Selective Anticancer Agents
2003
Chemistry and Biology
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While many investigators have fo-this elegant synthetic lethal approach to a higher level. ...
By compound National Cancer Institute diversity collection analogy, in a synthetic lethal chemical screen one looks has a substantial number of agents that interact with for killing only when cells have ...
Synthetic Lethal Strategy Used in Yeast Genetics Studies seems likely that many others will emulate their approach. ...
doi:10.1016/s1074-5521(03)00129-7
pmid:12837378
fatcat:qx6xepijcbazhn52nnbud6rc7y
Synthetic Lethal Networks for Precision Oncology: Promises and Pitfalls
2018
Journal of Molecular Biology
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Synthetic lethal interactions, in which the simultaneous loss-of-function of two genes produces a lethal phenotype, are being explored as a means to therapeutically exploit cancer-specific vulnerabilities ...
Currently, three FDA approved drugs work by targeting the synthetic lethal interaction between BRCA1/2 and PARP. ...
Shen) and a Career Development Grant from the Tower Cancer Research Foundation to J.P. Shen ...
doi:10.1016/j.jmb.2018.06.026
pmid:29932943
pmcid:PMC6097899
fatcat:izai2wrc4jezbaj2vzcms7623a
Synthetic Lethal Vulnerabilities in KRAS-Mutant Cancers
2017
Cold Spring Harbor Perspectives in Medicine
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Here, we review the compendium of previously identified codependencies in KRAS-mutant cancers, including the results of numerous functional genetic screens aimed at identifying KRAS synthetic lethal targets ...
An alternative therapeutic strategy for KRAS-mutant malignancies involves targeting codependent vulnerabilities or synthetic lethal partners that are preferentially essential in the setting of oncogenic ...
Whereas the long-sought-after universal synthetic lethal target for all KRAS-mutant cancers has not yet been identified, these studies have informed our understanding of KRAS biology and have identified ...
doi:10.1101/cshperspect.a031518
pmid:29101114
pmcid:PMC5990478
fatcat:lmvu3aihgrdtzerwhkbk2wmdta
Identification of potential synthetic lethal genes to p53 using a computational biology approach
2013
BMC Medical Genomics
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Methods: To illustrate this approach, we identified potentially druggable genes synthetically lethal for p53 using three microarray datasets for gene expression profiles of the NCI-60 cancer cell lines ...
Identification of potential synthetic lethal genes to p53 using a computational biology approach" (2013). Public Health Resources. 285. ...
Joel Bader for their valuable comments which greatly helped us to improve the manuscript. ...
doi:10.1186/1755-8794-6-30
pmid:24025726
pmcid:PMC3847148
fatcat:t43vywxuqjfzbpk6uvtrxpg3be
Synthetic Lethality in Cancer Therapeutics
2017
Annual Review of Cancer Biology
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We also discuss strategies for using synthetic lethality to discover new drug targets and in the rational design of more potent drug combinations. ...
Here we discuss both the experimental and the computational biology tools that can be used to identify synthetic lethal interactions. ...
The work of the authors was supported by grants from the Dutch Cancer Society (KWF), the Netherlands Organization for Scientific Research (NWO) through the Center for Cancer Genomics, and the European ...
doi:10.1146/annurev-cancerbio-042016-073434
fatcat:ljsesel32nh6npuarjo7nrig2e
Synthetic Lethality in Lung Cancer—From the Perspective of Cancer Genomics
2019
Medicines
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We highlight the potential challenges in synthetic lethal anticancer therapeutics that target untreatable genetic alterations in lung cancer. ...
The "synthetic lethal" approach holds the promise of delivering a therapeutic regimen that preferentially targets malignant cells while sparing normal cells. ...
Fumihiko Urabe for composing the manuscript structure.
Conflicts of Interest: The authors declare no conflict of interest. ...
doi:10.3390/medicines6010038
pmid:30871030
pmcid:PMC6473893
fatcat:tyxblzuf3nbgnjlkyyalb7u46q
SL-Cloud: A Cloud-based resource to support synthetic lethal interaction discovery
2022
F1000Research
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Synthetic lethal interactions (SLIs), genetic interactions in which the simultaneous inactivation of two genes leads to a lethal phenotype, are promising targets for therapeutic intervention in cancer, ...
We present SL-Cloud, a new component of the Institute for Systems Biology Cancer Gateway in the Cloud (ISB-CGC), that provides an integrated framework of cloud-hosted data resources and curated workflows ...
Institute for Systems Biology Cancer Gateway in the Cloud (ISB-CGC). ...
doi:10.12688/f1000research.110903.1
fatcat:yo47jv276rf2noafyn5a764gmm
Towards a more precise therapy in cancer: Exploring epigenetic complexity
2020
Current Opinion in Chemical Biology
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By exploring these challenges, among others, the field of epigenetic chemical biology will increase its potential for clinical benefit, and more effective strategies targeting the aberrant epigenome in ...
Specifically, we focus on the development of dual hybrids to exploit multitargeting of key epigenetic molecules deregulated in cancer; the study of epigenetic-synthetic lethality interactions as a mechanism ...
Funding The authors thank CERCA Programme/Generalitat de Catalunya for institutional support. ...
doi:10.1016/j.cbpa.2020.04.008
pmid:32480315
fatcat:4shxbu6wqffzre5cfvqlhicy5i
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