miRNAs and Target Genes in Breast Cancer Metastasis PDF
Preview miRNAs and Target Genes in Breast Cancer Metastasis
SPRINGER BRIEFS IN CANCER RESEARCH Seema Sethi miRNAs and Target Genes in Breast Cancer Metastasis 123 SpringerBriefs in Cancer Research For furthervolumes: http://www.springer.com/series/10786 ThiSisaFMBlankPage Seema Sethi miRNAs and Target Genes in Breast Cancer Metastasis SeemaSethi DepartmentofPathology WayneStateUniversitySchoolofMedicine KarmanosCancerInstitute Detroit,MI,USA ISBN978-3-319-08161-8 ISBN978-3-319-08162-5(eBook) DOI10.1007/978-3-319-08162-5 SpringerChamHeidelbergNewYorkDordrechtLondon LibraryofCongressControlNumber:2014943913 ©SpringerInternationalPublishingSwitzerland2014 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpart of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionor informationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar methodologynowknownorhereafterdeveloped.Exemptedfromthislegalreservationarebriefexcerpts inconnectionwithreviewsorscholarlyanalysisormaterialsuppliedspecificallyforthepurposeofbeing enteredandexecutedonacomputersystem,forexclusiveusebythepurchaserofthework.Duplication ofthispublicationorpartsthereofispermittedonlyundertheprovisionsoftheCopyrightLawofthe Publisher’s location, in its current version, and permission for use must always be obtained from Springer.PermissionsforusemaybeobtainedthroughRightsLinkattheCopyrightClearanceCenter. ViolationsareliabletoprosecutionundertherespectiveCopyrightLaw. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexempt fromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. While the advice and information in this book are believed to be true and accurate at the date of publication,neithertheauthorsnortheeditorsnorthepublishercanacceptanylegalresponsibilityfor anyerrorsoromissionsthatmaybemade.Thepublishermakesnowarranty,expressorimplied,with respecttothematerialcontainedherein. Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) To my parents, Sadanand and Tripta Bahri, whotaughtmetheimportanceofsincerehard work in making a difference in this world. Losing my father to cancer and knowing the pain, anguish, and turmoil of this disease motivated me to work in this field. To my husband Anil and children Aisha, Prajit, and Sajiv who all make it worthwhile. ThiSisaFMBlankPage Contents 1 Introduction:RoleofmiRNAsandTheirTargetGenesinBreast CancerMetastasis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 SeemaSethi,ShadanAli,andFazlulH.Sarkar 2 MolecularPathogenesisofBreastCancerandtheRoleof MicroRNAs. . . .. . . . . . . . .. . . . . . . . .. . . . . . . .. . . . . . . . .. . . . . . 7 ShadanAli,SeemaSethi,AzfurS.Ali,PhilipA.Philip,andFazlulH.Sarkar 3 Epidemiology,RiskFactors,Treatment,andPreventionofBreast CancerMetastases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 ManalNizam,SabaHaq,ShadanAli,RaaginiSuresh, RamziM.Mohammad,andFazlulH.Sarkar 4 ClinicalPerspectives:BreastCancerBrainMetastasis. . . . . . . . . . . . 37 SharonK.Michelhaugh,AlicciaBollig-Fischer,andSandeepMittal 5 ClinicalPerspectives:BreastCancerBoneMetastasis. . . . . . . . . . . . 53 AllenKadado,AnilSethi,andRahulVaidya 6 MolecularTargetedTherapyforBrainMetastaticBreastCancers: CurrentUpdates. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 AamirAhmadandFazlulH.Sarkar Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 vii Chapter 1 Introduction: Role of miRNAs and Their Target Genes in Breast Cancer Metastasis SeemaSethi,ShadanAli,andFazlulH.Sarkar Keywords Breastcancer(cid:129)miRNA(cid:129)Brainmetastasis(cid:129)Bonemetastasis BreastcanceristhemostcommoncanceramongwomenintheUnitedStatesand the second leading cause of cancer deaths among women of allages [1].In 2013, there have been approximately 232,340 new cases of invasive breast cancer and 39,620 breast cancer deaths among US women [2]. One out of 8 women in the UnitedStateswilldevelopbreastcancerinherlifetime[2]. Rapidadvancesinthefieldsofmolecularbiologyandmedicinehaveledtothe developmentofnoveltherapeuticstrategies forbreast cancer.Thesehave ledtoa significantimprovementintheprognosisofthisdiseasefromthepastfewdecades. Patients today have a wide range of therapeutic options including multimodality treatmentprotocolswithsurgery,chemotherapy,andmoleculartargetedtherapies. Molecular-basedtherapiesliketrastuzumab,targetingagainstHER2/neu,haveled toimprovedoutcomesinthesepatients. Although the prognosis has considerably improved for early stage cancers, unfortunately many patients die as a consequence of metastasis. It has been determined that approximately 25–40 % of patients develop metastatic disease which is generally incurable [3]. The metastasis could be at several body sites including the bone and brain. Once the metastasis develops, it heralds a rapid downhillcoursefor these patients. Notonlyisthe mortality increasedbutthere is significantmorbidity,impactingthequalityoflifeofthepatient. Metastatic disease dramatically reduces the 5-year survival by 20 % when compared with patients with no metastasis [4]. Once breast cancer has S.Sethi(*)(cid:129)F.H.Sarkar DepartmentofPathology,KarmanosCancerInstitute,WayneStateUniversity,Detroit,MI,USA e-mail:[email protected] S.Ali DepartmentofOncology,KarmanosCancerInstitute,WayneStateUniversity,Detroit,MI,USA ©SpringerInternationalPublishingSwitzerland2014 1 S.Sethi,miRNAsandTargetGenesinBreastCancerMetastasis, SpringerBriefsinCancerResearch,DOI10.1007/978-3-319-08162-5_1 2 S.Sethietal. metastasized, it becomes life threatening, the prognosis worsens, and patients require systemic treatment. Associated with reduction in the life span of patients are increasing side effects of therapies including chemo- and radiotherapeutic regimens towhich the patient becomes unresponsiveover time and the escalating healthcare costs, which become important for individual patients but become a majorsocialandeconomicproblem. Thebreastcancer-relatedmortalityandmorbidityisprimarilyduetometastatic disease, especially metastatic disease into the brain and bone [5], which is a complexpathologicphenomenonoccurringthroughastepwiseprogressioninclud- ing invasion of surrounding stromal tissue, intravasation, evasion of programmed cell death (apoptosis), arrest in a vessel at a distant site, extravasation and subse- quent establishment, and growth of the tumor at the site of metastasis (secondary growth in the metastatic milieu) [6–12]. The pathogenesis of these histological alterationsinbreastcanceriscomplex.Thenaturalhistoryofprogressionofbreast cancers to cause brain and bone metastasis has several proposed mechanisms. However,theexactunderlyingmolecularmechanismsarelargelyunknown. Metastasis is a key hallmark of breast cancer and occurs when cancer cells accesslymphaticandvascularsystemsanddisseminatevialymphnodesandthen viathevenousandarterialvascularsystemtodistantorgans.Mechanisticinsights into the pathologic development of metastasis at the molecular level could be helpfulinunderstandingthekeypathwaysimplicatedinthisprocess.Understand- ing of the biological processes of metastasis would empower us with the clinical knowledgeneededtoidentifyanddeveloptargetsforimplementingtherapeuticand preventive strategies against future development of metastasis, with the eventual goalofimprovingpatientsurvivalandqualityoflife. Anotherimportantaspectofrecognizingmetastasisisthetimewhenthemetas- tasiscouldoccur.Atpresentwecannotidentifywhichpatientswilllikelydevelop metastasisatwhichsiteandwhen.Thereisnofixedtimeperiodwhenthisprocess begins. Metastatic relapse typicallyoccursmanymonthstodecadesafter surgery. Understanding of the processes that arise following tumor-cell dissemination including the phenomenon of dormancy would be helpful in early detection of metastasisinthisdisease,andidentifyinghowtumorcellscanbekeptinastateof dormancy would provide strategies for management of this disease. Additional understanding is also needed in identifying the “pre-metastatic niches” in organs destinedtodevelopmetastases,whichareproposedtogeneratemetastases. Furtheralterationsatthemolecularlevelhavealsobeenusedforthemolecular subclassification of breast cancer [13–17]. Certain tumor characteristics, e.g., mesenchymal/stromal gene signatures, have been related to some breast cancer subtypes (e.g., triple negative breast tumors), bone metastasis, and resistance to neoadjuvanttherapies[18].Thepathologicdevelopmentandprogressionofbreast cancer seems to be a process-in-continuum which involves several molecular alterationsatthegenetic,epigenetic,andmiRNA level,leadingtoaclonalevolu- tion of malignant cells, and this process continues during metastatic progression. Breast oncogenesis, tumor progression, and development of metastasis involve deregulationofseveralprocesses.
The list of books you might like
