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dc.contributor.authorBlock, Keith Ien
dc.contributor.authorGyllenhaal, Charlotteen
dc.contributor.authorLowe, Leroyen
dc.contributor.authorAmedei, Amedeoen
dc.contributor.authorAmin, ARM Ruhulen
dc.contributor.authorAmin, Amren
dc.contributor.authorAquilano, Katiaen
dc.contributor.authorArbiser, Jacken
dc.contributor.authorArreola, Alexandraen
dc.contributor.authorArzumanyan, Allaen
dc.contributor.authorAshraf, S Salmanen
dc.contributor.authorAzmi, Asfar Sen
dc.contributor.authorBenencia, Fabianen
dc.contributor.authorBhakta, Dipitaen
dc.contributor.authorBilsland, Alanen
dc.contributor.authorBishayee, Anupamen
dc.contributor.authorBlain, Stacy Wen
dc.contributor.authorBlock, Penny Ben
dc.contributor.authorBoosani, Chandra Sen
dc.contributor.authorCarey, Thomas Een
dc.contributor.authorCarnero, Amancioen
dc.contributor.authorCarotenuto, Marianeveen
dc.contributor.authorCasey, Stephanie Cen
dc.contributor.authorChakrabarti, Mrinmayen
dc.contributor.authorChaturvedi, Rupeshen
dc.contributor.authorChen, Georgia Zhuoen
dc.contributor.authorChen, Helenen
dc.contributor.authorChen, Sophieen
dc.contributor.authorChen, Yi Charlieen
dc.contributor.authorChoi, Beom Ken
dc.contributor.authorCiriolo, Maria Rosaen
dc.contributor.authorColey, Helen Men
dc.contributor.authorCollins, Andrew Ren
dc.contributor.authorConnell, Marisaen
dc.contributor.authorCrawford, Sarahen
dc.contributor.authorCurran, Colleen Sen
dc.contributor.authorDabrosin, Charlottaen
dc.contributor.authorDamia, Giovannaen
dc.contributor.authorDasgupta, Santanuen
dc.contributor.authorDeBerardinis, Ralph Jen
dc.contributor.authorDecker, William Ken
dc.contributor.authorDhawan, Punitaen
dc.contributor.authorDiehl, Anna Mae Een
dc.contributor.authorDong, Jin-Tangen
dc.contributor.authorDou, Q Pingen
dc.contributor.authorDrew, Janice Een
dc.contributor.authorElkord, Eyaden
dc.contributor.authorEl-Rayes, Basselen
dc.contributor.authorFeitelson, Mark Aen
dc.contributor.authorFelsher, Dean Wen
dc.contributor.authorFerguson, Lynnette Ren
dc.contributor.authorFimognari, Carmelaen
dc.contributor.authorFirestone, Gary Len
dc.contributor.authorFrezza, Christianen
dc.contributor.authorFujii, Hiromasaen
dc.contributor.authorFuster, Mark Men
dc.contributor.authorGenerali, Danieleen
dc.contributor.authorGeorgakilas, Alexandros Gen
dc.contributor.authorGieseler, Franken
dc.contributor.authorGilbertson, Michaelen
dc.contributor.authorGreen, Michelle Fen
dc.contributor.authorGrue, Brendanen
dc.contributor.authorGuha, Gunjanen
dc.contributor.authorHalicka, Dorotaen
dc.contributor.authorHelferich, William Gen
dc.contributor.authorHeneberg, Petren
dc.contributor.authorHentosh, Patriciaen
dc.contributor.authorHirschey, Matthew Den
dc.contributor.authorHofseth, Lorne Jen
dc.contributor.authorHolcombe, Randall Fen
dc.contributor.authorHonoki, Kanyaen
dc.contributor.authorHsu, Hsue-Yinen
dc.contributor.authorHuang, Gloria Sen
dc.contributor.authorJensen, Lasse Den
dc.contributor.authorJiang, Wen Gen
dc.contributor.authorJones, Lee Wen
dc.contributor.authorKarpowicz, Phillip Aen
dc.contributor.authorKeith, W Nicolen
dc.contributor.authorKerkar, Sid Pen
dc.contributor.authorKhan, Gazala Nen
dc.contributor.authorKhatami, Mahinen
dc.contributor.authorKo, Young Hen
dc.contributor.authorKucuk, Omeren
dc.contributor.authorKulathinal, Rob Jen
dc.contributor.authorKumar, Nagi Ben
dc.contributor.authorKwon, Byoung Sen
dc.contributor.authorLe, Anneen
dc.contributor.authorLea, Michael Aen
dc.contributor.authorLee, Ho-Youngen
dc.contributor.authorLichtor, Terryen
dc.contributor.authorLin, Liang-Tzungen
dc.contributor.authorLocasale, Jason Wen
dc.contributor.authorLokeshwar, Bal Len
dc.contributor.authorLongo, Valter Den
dc.contributor.authorLyssiotis, Costas Aen
dc.contributor.authorMacKenzie, Karen Len
dc.contributor.authorMalhotra, Meenakshien
dc.contributor.authorMarino, Mariaen
dc.contributor.authorMartinez-Chantar, Maria Len
dc.contributor.authorMatheu, Anderen
dc.contributor.authorMaxwell, Christopheren
dc.contributor.authorMcDonnell, Eoinen
dc.contributor.authorMeeker, Alan Ken
dc.contributor.authorMehrmohamadi, Mahyaen
dc.contributor.authorMehta, Kapilen
dc.contributor.authorMichelotti, Gregory Aen
dc.contributor.authorMohammad, Ramzi Men
dc.contributor.authorMohammed, Sulma Ien
dc.contributor.authorMorre, D Jamesen
dc.contributor.authorMuqbil, Irfanaen
dc.contributor.authorMuralidhar, Vinayaken
dc.contributor.authorMurphy, Mikeen
dc.contributor.authorNagaraju, Ganji Purnachandraen
dc.contributor.authorNahta, Ritaen
dc.contributor.authorNiccolai, Elenaen
dc.contributor.authorNowsheen, Somairaen
dc.contributor.authorPanis, Carolinaen
dc.contributor.authorPantano, Francescoen
dc.contributor.authorParslow, Virginia Ren
dc.contributor.authorPawelec, Grahamen
dc.contributor.authorPedersen, Peter Len
dc.contributor.authorPoore, Braden
dc.contributor.authorPoudyal, Deepaken
dc.contributor.authorPrakash, Satyaen
dc.contributor.authorPrince, Marken
dc.contributor.authorRaffaghello, Lizziaen
dc.contributor.authorRathmell, Jeffrey Cen
dc.contributor.authorRathmell, W Kimrynen
dc.contributor.authorRay, Swapan Ken
dc.contributor.authorReichrath, Jörgen
dc.contributor.authorRezazadeh, Sarallahen
dc.contributor.authorRibatti, Domenicoen
dc.contributor.authorRicciardiello, Luigien
dc.contributor.authorRobey, R Brooksen
dc.contributor.authorRodier, Francisen
dc.contributor.authorRupasinghe, HP Vasanthaen
dc.contributor.authorRusso, Gian Luigien
dc.contributor.authorRyan, Elizabeth Pen
dc.contributor.authorSamadi, Abbas Ken
dc.contributor.authorSanchez-Garcia, Isidroen
dc.contributor.authorSanders, Andrew Jen
dc.contributor.authorSantini, Danieleen
dc.contributor.authorSarkar, Malanchaen
dc.contributor.authorSasada, Tetsuroen
dc.contributor.authorSaxena, Neeraj Ken
dc.contributor.authorShackelford, Rodney Een
dc.contributor.authorKumara, HMC Shanthaen
dc.contributor.authorSharma, Dipalien
dc.contributor.authorShin, Dong Men
dc.contributor.authorSidransky, Daviden
dc.contributor.authorSiegelin, Markus Daviden
dc.contributor.authorSignori, Emanuelaen
dc.contributor.authorSingh, Neetuen
dc.contributor.authorSivanand, Sharanyaen
dc.contributor.authorSliva, Danielen
dc.contributor.authorSmythe, Carlen
dc.contributor.authorSpagnuolo, Carmelaen
dc.contributor.authorStafforini, Diana Men
dc.contributor.authorStagg, Johnen
dc.contributor.authorSubbarayan, Pochi Ren
dc.contributor.authorSundin, Tabethaen
dc.contributor.authorTalib, Wamidh Hen
dc.contributor.authorThompson, Sarah Ken
dc.contributor.authorTran, Phuoc Ten
dc.contributor.authorUngefroren, Hendriken
dc.contributor.authorHeiden, Matthew G Vanderen
dc.contributor.authorVenkateswaran, Vasundaraen
dc.contributor.authorVinay, Dass Sen
dc.contributor.authorVlachostergios, Panagiotis Jen
dc.contributor.authorWang, Zongweien
dc.contributor.authorWellen, Kathryn Een
dc.contributor.authorWhelan, Richard Len
dc.contributor.authorYang, Eddy Sen
dc.contributor.authorYang, Huanjieen
dc.contributor.authorYang, Xujuanen
dc.contributor.authorYaswen, Paulen
dc.contributor.authorYedjou, Clementen
dc.contributor.authorYin, Xinen
dc.contributor.authorZhu, Jiyueen
dc.contributor.authorZollo, Massimoen
dc.date.accessioned2016-02-16T16:32:36Z
dc.date.available2016-02-16T16:32:36Z
dc.date.issued2015-11-18en
dc.identifier.citationBlock et al. Seminars in Cancer Biology (2015). volume 35, Supplement: pp. S276-S304. DOI:10.1016/j.semcancer.2015.09.007en
dc.identifier.issn1044-579X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/253796
dc.description.abstractTargeted therapies and the consequent adoption of “personalized” oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity “broad-spectrum” therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered.
dc.description.sponsorshipMultiple funders. See acknowledgments within article for details.
dc.languageEnglishen
dc.language.isoenen
dc.publisherElsevier
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.subjectmulti-targeteden
dc.subjectcancer hallmarksen
dc.subjectphytochemicalsen
dc.subjecttargeted therapyen
dc.subjectintegrative medicineen
dc.titleA broad-spectrum integrative design for cancer prevention and therapyen
dc.typeArticle
dc.provenanceOA-7042
dc.description.versionThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.semcancer.2015.09.007en
prism.endingPageS304
prism.publicationDate2015en
prism.publicationNameSeminars in Cancer Biologyen
prism.startingPageS276
prism.volume35en
dcterms.dateAccepted2015-09-14en
rioxxterms.versionofrecord10.1016/j.semcancer.2015.09.007en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-11-18en
dc.contributor.orcidFrezza, Christian [0000-0002-3293-7397]
dc.contributor.orcidMurphy, Mike [0000-0003-1115-9618]
dc.identifier.eissn1096-3650
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12022/6)
pubs.funder-project-idMRC (MC_U105663142)
pubs.funder-project-idMRC (unknown)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales