Evidence map›Paper›PMID 27453043›Full record

ArticleMolecular cell2016

A Network of Conserved Synthetic Lethal Interactions for Exploration of Precision Cancer Therapy.

Rohith Srivas, John Paul Shen, Chih Cheng Yang, Su Ming Sun, Jianfeng Li, Andrew M Gross, James Jensen, Katherine Licon, Ana Bojorquez-Gomez, Kristin Klepper and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

91 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
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  7. Article
  8. Article
  9. Article
  10. Article
  11. Machine Learning Approaches for the Identification of Genetic Interactions.Methods in molecular biology (Clifton, N.J.) · 2025
    Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. WRN suppresses p53/PUMA-induced apoptosis in colorectal cancer with microsatellite instability/mismatch repair deficiency.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  20. Article

31 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Rohith SrivasDivision of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA; The Cancer Cell Map Initiative.
John Paul ShenDivision of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA; The Cancer Cell Map Initiative.
Chih Cheng YangFunctional Genomics Core, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Su Ming SunDepartment of Human Genetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, the Netherlands.
Jianfeng LiDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
Andrew M GrossBioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, USA.
James JensenBioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, USA.
Katherine LiconDivision of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.
Ana Bojorquez-GomezDepartment of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.
Kristin KlepperDivision of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Justin HuangBioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, USA.
Daniel PekinDivision of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Jia L XuDivision of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Huwate YeernaDivision of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Vignesh SivaganeshDivision of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Leonie KollenstartDepartment of Human Genetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, the Netherlands.
Haico van AttikumDepartment of Human Genetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, the Netherlands.
Pedro Aza-BlancFunctional Genomics Core, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Robert W SobolDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
Trey IdekerDivision of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA; The Cancer Cell Map Initiative. Electronic address: tideker@ucsd.edu.

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael Jackson · 1985 to 2026
$107.2M
SYNTHETIC SYSTEMSP50GM085764 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HASTY, JEFF M, IDEKER, TREY · 2010 to 2018
$23.3M
A Systems Approach to Mapping the DNA Damage ResponseR01ES014811 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2005 to 2021
$8.6M
GRADUATE TRAINING PROGRAM IN BIONFORMATICST32GM008806 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BAFNA, VINEET, REN, BING · 2001 to 2020
$6.2M
Comparative Analysis of Genetic Interaction NetworksR01GM084279 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY, KROGAN, NEVAN J · 2008 to 2017
$3.9M
Novel approaches to enhance tumor cell cytotoxicity of alkylating agentsR01CA148629 · NCI · UNIVERSITY OF SOUTH ALABAMA · PI SOBOL, ROBERT W · 2010 to 2021
$3.4M
NCI NIH HHS P30 CA030199NCI NIH HHS R01 CA148629NIEHS NIH HHS R01 ES014811NIGMS NIH HHS P50 GM085764NIGMS NIH HHS R01 GM084279NIGMS NIH HHS T32 GM008806
6 · The paper itself

Abstract

An emerging therapeutic strategy for cancer is to induce selective lethality in a tumor by exploiting interactions between its driving mutations and specific drug targets. Here we use a multi-species approach to develop a resource of synthetic lethal interactions relevant to cancer therapy. First, we screen in yeast ∼169,000 potential interactions among orthologs of human tumor suppressor genes (TSG) and genes encoding drug targets across multiple genotoxic environments. Guided by the strongest signal, we evaluate thousands of TSG-drug combinations in HeLa cells, resulting in networks of conserved synthetic lethal interactions. Analysis of these networks reveals that interaction stability across environments and shared gene function increase the likelihood of observing an interaction in human cancer cells. Using these rules, we prioritize ∼10(5) human TSG-drug combinations for future follow-up. We validate interactions based on cell and/or patient survival, including topoisomerases with RAD17 and checkpoint kinases with BLM.

Indexed as

Genes, Tumor SuppressorMutationAntineoplastic AgentsBiomarkers, TumorCell Cycle ProteinsCell ProliferationCell SurvivalDose-Response Relationship, DrugFemaleGene Expression Regulation, FungalGene Expression Regulation, NeoplasticGene Regulatory NetworksGenetic Predisposition to DiseaseHeLa CellsHumansKaplan-Meier EstimateAntineoplastic AgentsBiomarkers, TumorBloom syndrome proteinCell Cycle ProteinsRad17 protein, humanRecQ HelicasesSaccharomyces cerevisiae Proteins

Identifiers

PMID27453043
PMCPMC5209245

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.