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dc.contributor.authorMatos, Bárbara
dc.contributor.authorHowl, John
dc.contributor.authorJerónimo, Carmen
dc.contributor.authorFardilha, Margarida
dc.date.accessioned2020-08-26T15:48:38Z
dc.date.available2020-08-26T15:48:38Z
dc.date.issued2020-08-16
dc.identifier.citationMatos, B., Howl, J., Jerónimo, C., Fardilha, M. (2020) The disruption of protein-protein interactions as a therapeutic strategy for prostate cancer, Pharmacological Research, 161 Article Number 105145. https://doi.org/10.1016/j.phrs.2020.105145en
dc.identifier.issn1043-6618en
dc.identifier.doi10.1016/j.phrs.2020.105145en
dc.identifier.urihttp://hdl.handle.net/2436/623520
dc.descriptionThis is an accepted manuscript of an article published by Elsevier in Pharmacological Research on 16/08/2020, available online: https://doi.org/10.1016/j.phrs.2020.105145 The accepted version of the publication may differ from the final published version.en
dc.description.abstractProstate cancer (PCa) is one of the most common male-specific cancers worldwide, with high morbidity and mortality rates associated with advanced disease stages. The current treatment options of PCa are prostatectomy, hormonal therapy, chemotherapy or radiotherapy, the selection of which is usually dependent upon the stage of the disease. The development of PCa to a castration-resistant phenotype (CRPC) is associated with a more severe prognosis requiring the development of a new and effective therapy. Protein-protein interactions (PPIs) have been recognised as an emerging drug modality and targeting PPIs is a promising therapeutic approach for several diseases, including cancer. The efficacy of several compounds in which target PPIs and consequently impair disease progression were validated in phase I/II clinical trials for different types of cancer. In PCa, various small molecules and peptides proved successful in inhibiting important PPIs, mainly associated with the androgen receptor (AR), Bcl-2 family proteins, and kinases/phosphatases, thus impairing the growth of PCa cells in vitro. Moreover, a majority of these compounds require further validation in vivo and, preferably, in clinical trials. In addition, several other PPIs associated with PCa progression have been identified and now require experimental validation as potential therapeutic loci. In conclusion, we consider the disruption of PPIs to be a promising though challenging therapeutic strategy for Pca. Agents which modulate PPIs might be employed as a monotherapy or as an adjunct to classical chemotherapeutics to overcome drug resistance and improve efficacy. The discovery of new PPIs with important roles in disease progression, and of novel optimized strategies to target them, are major challenges for the scientific and pharmacological communities.en
dc.description.sponsorshipWe thank the Portuguese Foundation for Science and Technology(FCT), European Union, QREN, FEDER and COMPETE for funding iBiMED (UIDB/04501/2020, POCI-01-0145-FEDER-23007628 and UID/BIM/04501/2019) and an individual scholarship from BM (SFRH/BD/146032/2019).en
dc.formatapplication/pdfen
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urlhttps://www.sciencedirect.com/science/article/abs/pii/S1043661820314535en
dc.subjectprotein-protein interactionsen
dc.subjectprostate canceren
dc.subjectpeptidesen
dc.titleThe disruption of protein-protein interactions as a therapeutic strategy for prostate canceren
dc.typeJournal articleen
dc.identifier.journalPharmacological Researchen
dc.date.updated2020-08-12T10:06:48Z
dc.identifier.articlenumber105145
dc.date.accepted2020-08-12
rioxxterms.funderPortuguese Foundation for Science and Technology(FCT), European Union, QREN, FEDER and COMPETEen
rioxxterms.identifier.projectUIDB/04501/2020en
rioxxterms.identifier.projectUID/BIM/04501/2019en
rioxxterms.identifier.projectPOCI-01-0145-FEDER-007628en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
rioxxterms.licenseref.startdate2021-08-16en
dc.source.volume161
refterms.dateFCD2020-08-26T15:46:23Z
refterms.versionFCDAM


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