其它抗肿瘤药

(K15A)THERAPEUTICDEFINITIONSCancerisacollectivetermencompassingover200diseaseswhichvarywidelyincause,molecularidentity,mannerofdevelopmentandrateofprogression.Itisanacquiredgeneticdisordercharacterizedbytheunregulatedandabnormalgrowthofcells,andcanpresentalmostanywhereinthebody.Alltypesofcancersharecertainbasicproperties:theircellsareabletoproliferateundetectedbytheimmunesystem,andunrestrictedbynormalcellcyclecontrolsandcell-cellinteractions.Cancercellsoftenalsofailtodifferentiateproperly,resultinginlossoffunction.Cancersaremalignant'neoplasms'(growths)thatcanbedistinguishedfrombenigngrowthsbytheirabilitytobreakoffandspreadfromtheoriginaltumour,toinvadeanddestroyotherhealthytissues.Thisistheprocessofmetastasis.Theresultantsecondarytumours(metastases)areoftenmoredifficulttotreatthantheoriginaltumour,andaretheusualcauseofdeathbycancer.Ifdetectedearlyenough,manycancersarecurable;equally,manyremainundiagnoseduntilanadvancedstageandareoftenfatal.Cancersaretypicallyclonal(arisingfromasinglecell),buttheprocessofoncogenesisisthoughttobemultistage,requiringthecelltoundergoaseriesofgeneticorepigeneticeventsultimatelyleadingtotheactivationofanoncogene,orconversely,theinactivationofatumoursuppressorgene.Theseeventscanbecausedbyexogenousorendogenousinfluences.Exogenousriskfactorsincludecertainlifestylechoicessuchassmoking,alcoholconsumption,sunexposureanddiet.Thereisalsoawellestablishedlinkbetweencertaininfectionsandcertaincancers:HPVandcervicalcancer,Helicobacterpyloriandgastriccancer,HBVandlivercancer.Endogenousfactorsincludehormonelevelsandinheritedgeneticmutations.Somepeoplemayhaveageneticpropensitytodevelopacertaintypeofcancerasaresult,forexample,ofinheritingadamagedcopyofatumoursuppressorgene.However,themostsignificantriskfactorfordevelopingcancerisage:70%ofallnewcasesarediagnosedinthoseovertheageof60.Cancersareclassifiedinavarietyofways.Theseinclude:bythetypeofcell(forexample,squamouscell),thetypeoftissue(forexample,sarcoma)andthesiteoforigin(forexample,lung).Theseverityandextentofacanceraredescribedusingthestagingsystem.Cancersareclassifiedasstage0,I,II,IIIorIV,wherestage0isanoninvasiveinsitucarcinomawithnolymphnodeinvolvementormetastasis,andstageIVisatumourofanysizewithanyleveloflymphnodeinvolvement,andmetastasespresent.Cancersthatdonotarisefromthebonemarroworlymphaticsystemareknownas'solidtumours'.Worldwide,themostcommontypesofcancerarethoseofthelung,breast,colon,prostate,liver,oesophagus,stomachandcervix.Thestapletreatmentsforcanceraresurgery,radiotherapy,chemotherapyandhormonaltherapy.Chemotherapyisusedascurative,adjuvantorpalliativetreatmentforsystemiccancers.OtherthanagentsthatactbyalkylatingDNA(K1B),cytotoxicagentsderivedfromantibiotics(K1A),anddrugsthatinterferewithcellmetabolism(K1C),chemotherapeuticsincludetopoisomeraseandmicrotubuleinhibitors,retinoidsandnewerdrugswhichactontyrosinekinasegrowthfactorreceptors.Useofchemotherapeuticsisoftenfrustratedbydose-limitingtoxicside-effectsandthedevelopmentofdrugresistance.Inrecentyears,emphasishasshiftedtothedevelopmentofmoretargetedandlesscytotoxicapproaches,anddrugsunderdevelopmentinthiscategoryincludethosedesignedtotargetcellcycleenzymes,chemokinesandcytokines,celladhesionmolecules(integrinsandmatrixmetalloproteinases),growthfactorsandtheirreceptors,andmoleculesinvolvedinangiogenesisandapoptosis.Thissectionincludesallgeneralanticanceragentsforwhichthemodeofactionisunknownorthosewhichdonotcomeundertheotheranticancercategories(exceptRadio/chemosensitizer(K5A)andRadio/chemoprotective(K5B)).UpdatedbyAGon10/4/2007.INCIDENCESANDMARKETVALUESCancer,basalcellDESCRIPTIONVALUEAREASOURCEIncidence800,000/yrTheUSTheSkinCancerFoundationWebPage,8Apr2005Incidence2,000,000/yrWorldwidePressrelease,PhotoCure,25Nov2003Cancer,biliaryDESCRIPTIONVALUEAREASOURCEIncidencein2008(estimate)9,520TheUSCancerFactsandFigures2008,AmericanCancerSocietyMortalityin2008(estimate)3,340TheUSCancerFactsandFigures2008,AmericanCancerSocietyCancer,bladderDESCRIPTIONVALUEAREASOURCEIncidencein2008(estimate)68,810TheUSCancerFactsandFigures2008,AmericanCancerSocietyMortalityin2008(estimate)14,100TheUSCancerFactsandFigures2008,AmericanCancerSocietyCancer,boneDESCRIPTIONVALUEAREASOURCEIncidencein2008(estimate)2,380TheUSCancerFactsandFigures2008,AmericanCancerSocietyMortalityin2008(estimate)1,470TheUSCancerFactsandFigures2008,AmericanCancerSocietyCancer,brainDESCRIPTIONVALUEAREASOURCEIncidencein2008(estimate)21,810TheUSCancerFactsandFigures2008,AmericanCancerSocietyMortalityin2008(estimate)13,070TheUSCancerFactsandFigures2008,AmericanCancerSociety5yrsurvivalrate32.2%TheUSCentralBrainTumorRegistryoftheUnitedStatesWebPage,9Feb2004Cancer,breastDESCRIPTIONVALUEAREASOURCEIncidencein2008(esitmate)184,450TheUSCancerFactsandFigures2008,AmericanCancerSocietyMortalityin2008(estimate)40,930TheUSCancerFactsandFigures2008,AmericanCancerSocietyCancer,cervicalDESCRIPTIONVALUEAREASOURCEPrevalence1.7millionWorldwideCompanyWebPage,Xenova,30Jan2004Incidence450,000/yrWorldwideCompanyWebPage,Xenova,30Jan2004Incidencein20078(esti