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dc.contributor.authorFrezza, Christianen
dc.date.accessioned2016-05-24T14:50:56Z
dc.date.available2016-05-24T14:50:56Z
dc.date.issued2016-05-18en
dc.identifier.issn1552-4450
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/256083
dc.description.abstractCancer cells are biosynthetic factories that gear multiple metabolic pathways toward cell growth and proliferation. Serine is the metabolite consumed third most by cancer cells, after glucose and glutamine, and is used as a building block for proteins and as a carbon donor for nucleotide biosynthesis. Serine can also be synthesized de novo from glucose (Fig. 1, left). Studies in the late 1980s demonstrated that de novo synthesis of serine is increased in cancer cells, suggesting that this pathway might be relevant for their growth. But it was not until the landmark discovery thatphosphoglycerate dehydrogenase (encoded by PHGDH), the first step of de novo serine synthesis, is genomically amplified in breast cancer and melanoma that this pathway came into the limelight. Importantly, silencing PHGDH in PHGDH-dependent cancers significantly affects their growth, making this enzyme an excellent target for cancer therapy. Recent work from Mullarky et al. reported the discovery of a novel noncompetitive inhibitor of PHGDH. However, although this compound was selective against PHGDH-dependent melanoma and breast cancer cell lines, it was unstable in mouse plasma, limiting its use in vivo. In this issue of Nature Chemical Biology, Pacold et al. report the discovery of small-molecule inhibitors of PHGDH that exhibit potent antitumor activity both in vitro an in vivo.
dc.languageEnglishen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.subjectcancer therapyen
dc.subjectmetabolic pathwaysen
dc.subjectmetabolomicsen
dc.subjectsmall moleculesen
dc.titleCancer metabolism: Addicted to serineen
dc.typeArticle
dc.description.versionThis is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nchembio.2086en
prism.endingPage390
prism.publicationDate2016en
prism.publicationNameNature Chemical Biologyen
prism.startingPage389
prism.volume12en
dc.identifier.doi10.17863/CAM.19
dcterms.dateAccepted2016-04-13en
rioxxterms.versionofrecord10.1038/nchembio.2086en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2016-05-18en
dc.contributor.orcidFrezza, Christian [0000-0002-3293-7397]
dc.identifier.eissn1552-4469
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12022/1_do not transfer?)
pubs.funder-project-idMedical Research Council (MC_UU_12022/6)
rioxxterms.freetoread.startdate2016-11-18


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