通过控制癌前病变拦截癌症

发布时间：2021-08-10 09:14:38来源：肿瘤免疫细胞治疗资讯

显而易见的是，已经转移或扩散到许多不同器官的癌症是难以治愈的。这些癌症通常包含数千个缺陷基因，此类缺陷基因导致恶性肿瘤并降低治疗效果。这些癌症能否在恶化之前被拦截？

许多最常见的癌症都会先发生癌前病变。癌前细胞虽然不能侵入器官和组织，也不能扩散到全身而危及生命，但与致命的癌细胞有许多共同的特点，如不受控制的生长。癌前细胞也会获得与病变癌症相似的基因缺陷。随着对这些基因缺陷的深入了解，治疗癌前病变可能是拦截癌症的最有希望的策略，即在癌症完全形成之前就进行早期干预，阻止其发生。

到目前为止，大多数成功的癌症预防措施都着力于将癌症发生中可避免的风险降至最低。人群研究已经确定了几种致癌原因，如吸烟、病毒感染、饮食或工作场所中的致癌物等，这使得有效的癌症预防成为可能。对遗传癌症倾向的研究已经发现了利用手术预防癌症的更多方法。例如，从乳房、卵巢和输卵管中切除虽正常但易患癌的组织，可以降低BRCA基因缺陷携带者的患癌风险。

本文作者WilliamG.Nelson,MD,PhD

"CancerToday"主编

英文原文如下

Clearly,cancersthathavemetastasized,orspread,tomanydifferentorgansitesaredifficulttocure.Thesecancerstypicallycontainthousandsofdefectivegenesthatdrivemalignancyandundermineattemptsattreatment.Canthesecancersbeinterceptedbeforetheyprogresstoamalignantstate?

Manyofthemostcommoncancersareheraldedbypremalignantconditions.Precancerouscells,thoughunabletoinvadeorgansandtissuesorspreadthroughoutthebodytothreatenlife,nonethelesssharemanyfeatureswithcellsinlife-threateningcancers,includinguncontrolledgrowth.Thepremalignantcellsalsoacquiregenedefectssimilartothoseseeninfull-blowncancers.Asthesegenedefectsarebetterunderstood,treatingpremalignancymayprovetobethemostpromisingtacticforcancerinterception—interveningearlytostopcancersbeforetheyfullydevelop.

Mostsuccessfulcancerpreventionthusfarhasfocusedonminimizingavoidablerisksforcancerdevelopment.Populationresearchhasidentifiedseveralcancercauses—suchascigarettesmoking,viralinfections,andcarcinogensinthedietorworkplace—andthishasenabledeffectivecancerprevention.Studiesofinheritedpredispositionstocancershaveidentifiedfurtheropportunitiesforcancerpreventionusingprophylacticsurgery.Asanexample,removalofotherwisehealthybutnonethelesscancer-pronetissuesfromthebreasts,ovaries,andfallopiantubescanreducecancerriskforcarriersofdefectiveBRCAgenes.

Cancerinterception,viathesystematictargetingofpremalignancy,offersachancetoconfrontanevengreaterrangeofcancertypes.Already,treatmentofpremalignantconditionshasproveneffectiveinreducingtheriskofdevelopingmanyfull-blowncancers.Drugsthattreatprecancerousconditionsofblood-formingcellscanlimitprogressiontoleukemiaormultiplemyeloma.Atsolidorgansites,precancerouslesionstendtoresemblecancersinmanyways.Althoughtheyareincapableofgrowinginvasively,theselesionscangiverisetoinvasivecancers.Forthisreason,iftheycanberemoved,theriskforlife-threateningcancerisoftenreduced.Removalofpolypsfromthecolontopreventcolorectalcancerisanexampleofthisapproach.

Tobesttacklepremalignancy,researchonthegenedefectsacquiredbyprecancerouscellsmustbeintensified.Justascataloguinggenedefectsinestablishedcancershasledtoprecisiontreatmentsguidedbythespecificgenealterationspresentinindividualcancercases,takinginventoryofgenealterationsinpremalignantlesionscouldleadtosimilarbenefits.Inaddition,thespectacularresponsesofsomemetastaticcancerstoimmunotherapyhighlighttheneedfordeeperstudiesofhowtheimmunesystemrecognizesandrespondstopremalignancy.Perhapsnewimmunotherapyapproachescouldreduceoreliminateprecancerouslesionsandotherprecancerousconditions.

RampingupresearchonpremalignancyoffersthebestresponsetoachallengeissuedalmostadecadeagobyElizabethBlackburn,PhD,aNobellaureateandPastPresidentoftheAmericanAssociationforCancerResearch,whichpublishesCancerToday:“Althoughtreatingorevencuringcancerisoften,understandably,attheforefrontofpeople’sminds,cancerwillneverbebroughtundercontrolunlesstheothersideoftheequationisaddressed:intercepting,orpreventing,it.”

WilliamG.Nelson,MD,PhD,istheeditor-in-chiefofCancerToday,thequarterlymagazineforcancerpatients,survivors,andcaregiverspublishedbytheAmericanAssociationforCancerResearch.NelsonistheMarionI.KnottprofessorofoncologyanddirectoroftheSidneyKimmelComprehensiveCancerCenteratJohnsHopkinsinBaltimore.Youcanreadhiscompletecolumninthewinter2020/2021issueofCancerToday.

发布于AACR官方博客《CancerResearchCatalyst》

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