biostudies-literatureBlock KIBLRD VAIntramural NIH HHSCancer Research UKNIA NIH HHSNCRR NIH HHSNIAID NIH HHSNIEHS NIH HHSNHLBI NIH HHSNatural Environment Research CouncilCIHRNCCIH NIH HHSNIDDK NIH HHSMedical Research CouncilNIMHD NIH HHSNCI NIH HHSNINDS NIH HHSNIAMS NIH HHSWellcome TrustNIGMS NIH HHSPHS HHSS276-S304https://www.ebi.ac.uk/biostudies/studies/S-EPMC4819002biostudies-literatureUnknown35 SupplTargeted 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 mecSeminars in cancer biologyDesigning a broad-spectrum integrative approach for cancer prevention and treatment.PMC4819002R01 CA109335R01 AI110613R01 CA120009CA164095R01 CA010951R01CA156776CA-10951MC_UU_12022/6R15 CA137499-01R21CA169757R01 HL108006U54CA143907P20 RR016477R21 CA184788T32HL098062P30 AG028716F31 CA154080K01DK0771375R01CA127258-05R01 CA151304P01 CA073992R01 CA109335-04A1F32CA177139R33 CA161873R01 CA166348CEH010010P20RR016477R01 CA170378P20 GM103434R01 AG045351G12 MD007581R01 CA028704R01HL108006R21CA188818AR47901K08 NS083732R01 HL107652R01CA166348R01 CA1567761R01CA20009C301/A14762P30AG028716-01R01GM071725R01 AG020642G1200MD007581F32 CA177139CA168997K01 DK077137R01 CA100816K08NS083732MC_U105663142R21 CA1888181R01CA151304I01 BX001517T32 CA059365P30 CA22453R01AG020642U54 CA143907T32 HL098062R01 GM071725R03DK089130K01AT007324ES019458R01CA100816R21 CA155686P20GM103434T32 HL1346321P01AT003961MSH-136647R01 CA127258R01 AR047901R21 CA169757R21CA184788P01 AG034906R01 CA164095R00 CA168997U54 CA149145R03 CA171326P30 CA008748R01CA1703781R03CA1711326R01CA131294AI076535U54CA149145K01 AT007324F31CA154080P30 CA022453P01 AT0039615T32-CA059365MOP114962R01 CA131294R33 CA161873-02P01AG0349065P01CA073992MOP125857T32-CA059365-19R01-HL107652U01 ES019458MC_UP_1101/3NCI NCIRO1 28704MOP 64308R01 AI076535R03 DK089130P01AG034906-01A1R15 CA137499DeBerardinis RJKhatami MChen YCEl-Rayes BDiehl AMEVinay DSAmedei ADrew JEHuang GSMaxwell CStagg JStafforini DMShin DMCrawford SHonoki KKucuk OSpagnuolo CPrince MSarkar MChen GZRaffaghello LFelsher DWHsu HYGuha GGilbertson MMorre DJKhan GNMatheu ADasgupta SGeorgakilas AGCarnero AConnell MHentosh PChaturvedi RLin LTLyssiotis CARibatti DHeneberg PMeeker AKRicciardiello LColey HMWellen KEPawelec GTalib WHArbiser JSidransky DAmin ASaxena NKNahta RPantano FMohammad RMShantha Kumara HMCCarey TEBhakta DArreola AKarpowicz PARay SKJones LWRupasinghe HPVZollo MSivanand SCurran CSYaswen PCiriolo MRLe ARobey RBMarino MSmythe CJensen LDTran PTPoore BSiegelin MDRathmell WKDhawan PDamia GPanis CSundin TZhu JElkord EKo YHHelferich WGKumar NBFujii HMehta KGenerali DSubbarayan PRYang ESHirschey MDSanders AJCasey SCSantini DDong JTVlachostergios PJAquilano KLichtor TNowsheen SDou QPSanchez-Garcia IBenencia FShackelford REPedersen PLMartinez-Chantar MLReichrath JChakrabarti MSharma DSingh NGrue BLowe LDecker WKChen SWang ZAmin ARMRLea MAYang HFuster MMRezazadeh SVander Heiden MGSamadi AKVenkateswaran VRusso GLLee HYParslow VRAzmi ASChen HSasada TMcDonnell EYang XRyan EPLokeshwar BLBilsland AKeith WNMuqbil IBlock PBMohammed SIRodier FMehrmohamadi MMalhotra MJiang WGKulathinal RJDabrosin CAshraf SSHalicka DGieseler FBlain SWFrezza CRathmell JCBlock KIMuralidhar VKerkar SPWhelan RLPrakash SThompson SKArzumanyan AMurphy MPCarotenuto MCollins ARLongo VDFimognari CFeitelson MAYin XFirestone GLGreen MFMacKenzie KLPoudyal DBoosani CSChoi BKFerguson LRSliva DHolcombe RFKwon BSNagaraju GPYedjou CGyllenhaal CBishayee ALocasale JWMichelotti GAUngefroren HHofseth LJNiccolai ESignori EfalseDesigning a broad-spectrum integrative approach for cancer prevention and treatment.Targeted 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 mec2015-01-01T00:00:00Z2015 Dec2025-05-29T22:26:46.659Z2020-10-29T13:20:02ZS-EPMC48190022659047710.1016/j.semcancer.2015.09.007