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Defeat mutant KRAS with synthetic lethality

Xiufeng Pang, Mingyao Liu
2016 Small GTPases  
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

Bingbing Dai, Bingliang Fang, Jack A. Roth
2009 Cancer Biology & Therapy  
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

Iñigo Apaolaza, Edurne San José-Eneriz, Xabier Agirre, Felipe Prósper, Francisco J. Planes
2017 Molecular & Cellular Oncology  
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

Jordan M Thompson, Quy H Nguyen, Manpreet Singh, Olga V Razorenova
2015 The Yale Journal of Biology and Medicine  
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

T.F. WESTBROOK, F. STEGMEIER, S.J. ELLEDGE
2005 Cold Spring Harbor Symposia on Quantitative Biology  
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

A. Ashworth, R. Bernards
2010 Cold Spring Harbor Perspectives in Biology  
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

Marta Roman, Elizabeth Hwang, E. Alejandro Sweet-Cordero
2022 Cancers  
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

John S Lazo
2003 Chemistry and Biology  
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

John Paul Shen, Trey Ideker
2018 Journal of Molecular Biology  
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

Andrew J. Aguirre, William C. Hahn
2017 Cold Spring Harbor Perspectives in Medicine  
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

Xiaosheng Wang, Richard Simon
2013 BMC Medical Genomics  
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

Roderick L. Beijersbergen, Lodewyk F.A. Wessels, René Bernards
2017 Annual Review of Cancer Biology  
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

Iwao Shimomura, Yusuke Yamamoto, Takahiro Ochiya
2019 Medicines  
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

Bahar Tercan, Guangrong Qin, Taek-Kyun Kim, Boris Aguilar, John Phan, William Longabaugh, David Pot, Christopher J. Kemp, Nyasha Chambwe, Ilya Shmulevich
2022 F1000Research  
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

Fernando P. Cossío, Manel Esteller, María Berdasco
2020 Current Opinion in Chemical Biology  
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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