Show simple item record

dc.contributor.authorCassidy, Johnen
dc.contributor.authorBatra, ASen
dc.contributor.authorGreenwood, Wendyen
dc.contributor.authorBruna, Alejandraen
dc.date.accessioned2016-12-08T15:23:30Z
dc.date.available2016-12-08T15:23:30Z
dc.date.issued2016-12-01en
dc.identifier.issn1351-0088
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/261495
dc.description.abstractDespite remarkable advances in our understanding of the drivers of human malignancies, new targeted therapies often fail to show sufficient efficacy in clinical trials. Indeed, the cost of bringing a new agent to market has risen substantially in the last several decades, in part fuelled by extensive reliance on preclinical models that fail to accurately reflect tumour heterogeneity. To halt unsustainable rates of attrition in the drug discovery process, we must develop a new generation of preclinical models capable of reflecting the heterogeneity of varying degrees of complexity found in human cancers. Patient-derived tumour xenograft (PDTX) models prevail as arguably the most powerful in this regard because they capture cancer's heterogeneous nature. Herein, we review current breast cancer models and their use in the drug discovery process, before discussing best practices for developing a highly annotated cohort of PDTX models. We describe the importance of extensive multidimensional molecular and functional characterisation of models and combination drug-drug screens to identify complex biomarkers of drug resistance and response. We reflect on our own experiences and propose the use of a cost-effective intermediate pharmacogenomic platform (the PDTX-PDTC platform) for breast cancer drug and biomarker discovery. We discuss the limitations and unanswered questions of PDTX models; yet, still strongly envision that their use in basic and translational research will dramatically change our understanding of breast cancer biology and how to more effectively treat it.
dc.description.sponsorshipThis work was supported by Cancer Research UK (grant number RG84936).
dc.languageENGen
dc.language.isoenen
dc.publisherbioscientifica
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectbreast canceren
dc.subjectdrug discoveryen
dc.subjectbiomarker discoveryen
dc.subjecthigh-throughput screeningen
dc.subjectpatient-derived tumour xenograftsen
dc.subjecttargeted therapiesen
dc.subjectpharmacogenomicsen
dc.titlePatient-derived tumour xenografts for breast cancer drug discoveryen
dc.typeArticle
prism.endingPageT270
prism.issueIdentifier12en
prism.publicationDate2016en
prism.publicationNameEndocrine-Related Canceren
prism.startingPageT259
prism.volume23en
dc.identifier.doi10.17863/CAM.6688
dcterms.dateAccepted2016-10-04en
rioxxterms.versionofrecord10.1530/ERC-16-0251en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2016-12-01en
dc.contributor.orcidGreenwood, Wendy [0000-0002-2509-8695]
dc.contributor.orcidBruna, Alejandra [0000-0003-1214-9665]
dc.identifier.eissn1479-6821
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (C14303_do not transfer)
pubs.funder-project-idMRC (G0300648)
cam.orpheus.successThu Jan 30 12:56:49 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International