Biological Activity of Lenalidomide and Its Underlying Therapeutic Effects in Multiple Myeloma英文文献资料.docVIP

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Biological Activity of Lenalidomide and Its Underlying Therapeutic Effects in Multiple Myeloma英文文献资料.doc

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Biological Activity of Lenalidomide and Its Underlying Therapeutic Effects in Multiple Myeloma英文文献资料

HindawiPublishingCorporation AdvancesinHematology Volume2012,ArticleID842945,11pages doi:10.1155/2012/842945 ReviewArticle BiologicalActivityofLenalidomideandItsUnderlying TherapeuticEffectsinMultipleMyeloma RobertaMartiniani,ValentinaDiLoreto,ChiaraDiSano, AlessandraLombardo,andAnnaMarinaLiberati DepartmentofOncohematology,UniversityofPerugia,SantaMariaHospital,05100Terni,Italy CorrespondenceshouldbeaddressedtoAnnaMarinaLiberati,marinal@unipg.it Received16February2012;Revised1May2012;Accepted2May2012 AcademicEditor:AgostinoCortelezzi Copyright?2012RobertaMartinianietal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly cited. Lenalidomideisasyntheticcompoundderivedbymodifyingthechemicalstructureofthalidomide.Itbelongstothesecond generationofimmunomodulatorydrugs(IMiDs)andpossessespleiotropicproperties.Eveniflenalidomidehasbeenshowntobe activeinthetreatmentofseveralhematologicmalignancies,thisreviewarticleismostlyfocalizedonitsmodeofactioninmultiple myeloma.Thepresentpaperisaboutthedirectandindirectantitumore?ectsoflenalidomideonmalignantplasmacells,bone marrowmicroenvironment,boneresorptionandhost’simmuneresponse.Themolecularmechanismsandtargetsoflenalidomide remainlargelyunknown,butrecentevidenceshowscereblon(CRBN)asapossiblemediatorofitstherapeuticale?ects. 1.Introduction to other B-cell neoplasia. The favourable toxic pro?le of lenalidomideanditsantitumoractivityemergedfromphase IandphaseIIstudiesinrelapsedorrefractoryMMpatients [23–25].Theseencouragingresultsledtothedesignoftwo large, phase III, multinational, randomized, double-blind, placebo-controlled, registration trials (MM-009 in US and CanadaandMM-010inEurope,Australia,andIsrael)inthis settingofpatients.Inbothstudies,patientswererandomly assigned to receive 25mg of lenalidomide or placebo on days 1 to 21 of 28-day cycles plus dexamethasone (40mg on days 1 to 4, 9 to 12 and 1