SwePub
Sök i LIBRIS databas

  Utökad sökning

WFRF:(Villanueva Alberto)
 

Sökning: WFRF:(Villanueva Alberto) > Cancer network acti...

  • Serra-Musach, JordiBellvitge Institute Biomed Research IDIBELL, Spain (författare)

Cancer network activity associated with therapeutic response and synergism

  • Artikel/kapitelEngelska2016

Förlag, utgivningsår, omfång ...

  • 2016-08-24
  • BIOMED CENTRAL LTD,2016
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:liu-131576
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-131576URI
  • https://doi.org/10.1186/s13073-016-0340-xDOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding Agencies|Generalitat de Catalunya AGAUR SGR [364]; Spanish Ministry of Health ISCIII [PI12/01528, PI15/00854, RTICC RD12/0036/0007, 0008]; Spanish Ministry of Science and Innovation "Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa" [PIE13/00022-ONCOPROFILE]; Telemaraton "Todos Somos Raros, Todos Somos Unicos" [P35]
  • Background: Cancer patients often show no or only modest benefit from a given therapy. This major problem in oncology is generally attributed to the lack of specific predictive biomarkers, yet a global measure of cancer cell activity may support a comprehensive mechanistic understanding of therapy efficacy. We reasoned that network analysis of omic data could help to achieve this goal. Methods: A measure of "cancer network activity" (CNA) was implemented based on a previously defined network feature of communicability. The network nodes and edges corresponded to human proteins and experimentally identified interactions, respectively. The edges were weighted proportionally to the expression of the genes encoding for the corresponding proteins and relative to the number of direct interactors. The gene expression data corresponded to the basal conditions of 595 human cancer cell lines. Therapeutic responses corresponded to the impairment of cell viability measured by the half maximal inhibitory concentration (IC50) of 130 drugs approved or under clinical development. Gene ontology, signaling pathway, and transcription factor-binding annotations were taken from public repositories. Predicted synergies were assessed by determining the viability of four breast cancer cell lines and by applying two different analytical methods. Results: The effects of drug classes were associated with CNAs formed by different cell lines. CNAs also differentiate target families and effector pathways. Proteins that occupy a central position in the network largely contribute to CNA. Known key cancer-associated biological processes, signaling pathways, and master regulators also contribute to CNA. Moreover, the major cancer drivers frequently mediate CNA and therapeutic differences. Cell-based assays centered on these differences and using uncorrelated drug effects reveals novel synergistic combinations for the treatment of breast cancer dependent on PI3K-mTOR signaling. Conclusions: Cancer therapeutic responses can be predicted on the basis of a systems-level analysis of molecular interactions and gene expression. Fundamental cancer processes, pathways, and drivers contribute to this feature, which can also be exploited to predict precise synergistic drug combinations.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Mateo, FrancescaBellvitge Institute Biomed Research IDIBELL, Spain (författare)
  • Capdevila-Busquets, EvaBarcelona Institute Science and Technology, Spain (författare)
  • Ruiz de Garibay, GorkaBellvitge Institute Biomed Research IDIBELL, Spain (författare)
  • Zhang, XiaohuNIH, MD 20850 USA (författare)
  • Guha, RajNIH, MD 20850 USA (författare)
  • Thomas, Craig J.NIH, MD 20850 USA (författare)
  • Grueso, JuditVHIO, Spain (författare)
  • Villanueva, AlbertoBellvitge Institute Biomed Research IDIBELL, Spain (författare)
  • Jaeger, SamiraBarcelona Institute Science and Technology, Spain (författare)
  • Heyn, HolgerIDIBELL, Spain (författare)
  • Vizoso, MiguelIDIBELL, Spain (författare)
  • Perez, HectorIDIBELL, Spain (författare)
  • Cordero, AlexIDIBELL, Spain (författare)
  • Gonzalez-Suarez, EvaIDIBELL, Spain (författare)
  • Esteller, ManelIDIBELL, Spain; University of Barcelona, Spain; University of Barcelona, Spain; ICREA, Spain (författare)
  • Moreno-Bueno, GemaAutonomous University of Madrid, Spain; MD Anderson Int Fdn, Spain (författare)
  • Tjärnberg, AndreasLinköpings universitet,Bioinformatik,Tekniska fakulteten(Swepub:liu)andtj33 (författare)
  • Lazaro, ConxiIDIBELL, Spain (författare)
  • Serra, VioletaVHIO, Spain (författare)
  • Arribas, JoaquinICREA, Spain; VHIO, Spain; Autonomous University of Barcelona, Spain (författare)
  • Benson, MikaelLinköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,Region Östergötland, Allergicentrum US(Swepub:liu)mikbe05 (författare)
  • Gustafsson, MikaLinköpings universitet,Bioinformatik,Tekniska fakulteten(Swepub:liu)mikgu75 (författare)
  • Ferrer, MarcNIH, MD 20850 USA (författare)
  • Aloy, PatrickBarcelona Institute Science and Technology, Spain; ICREA, Spain (författare)
  • Angel Pujana, MiquelBellvitge Institute Biomed Research IDIBELL, Spain (författare)
  • Bellvitge Institute Biomed Research IDIBELL, SpainBarcelona Institute Science and Technology, Spain (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Genome Medicine: BIOMED CENTRAL LTD8:881756-994X

Internetlänk

Hitta via bibliotek

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy