Ukuhlola ii-Biomarkers ezinokuthi zibikezele ukuba ubuchopho bakho buya kunciphisa
Ingcamango yokusebenzisa isistim somzimba womntu ukulwa nomhlaza ayikho inveli, kodwa ukufumana le ngcamango ukuguqulela kwindlela yokwelapha kuye kwaba yintlanzi yokulwa.
Iindaba ezilungileyo kukuba ngokuphumelela kutshanje kwezilwanyana ezibizwa ngokuba yi- immune checkpoint inhibitors , ukusetyenziswa kwe-immunotherapy ukunyanga umdlavuza kuye kwavuselelwa. Ngoku, ukongezelela ekuphuhliseni i-inhibitors yokujonga i-immune checkpoint, abaphandi bafumana iindlela zokwenza ngcono ukukhetha abaviwa abagqwesileyo kwezo ziyobisi.
Ngamanye amazwi, iingcali zifuna ukudibanisa kunye nezigulane ezinokuthi zizuze kulolu hlobo lwe-immunotherapy, okuthetha ukuba umdlavuza wabo unakho ukuphazamiseka okanye ulahleke ngenxa yolu hlobo unyango.
Iimpendulo azikho ngqo, ngoko kuyafaneleka ukuthatha ixesha elithile ukuqonda izinto ezisisiseko zophando oluqhubela phambili.
Impendulo kwi-Immune Checkpoint Blockade: i-Biomarkers
Abaphandi baphanda iindlela zokuchonga ukuba zeziphi iimpawu zokuzikhusela eziza kusebenza ngempumelelo kwisigulane ngasinye. Ngokufanelekileyo, i-oncologist (ugqirha ogqirha ukuphelisa umdlavuza) angathanda ukuvavanya amangqamuzana omhlaza womntu kwi-biomarker (okanye i-biomarker ezininzi).
Ezi zixhobo ziza kuxela ubungqina bomntu ukuba aphendule kwi-immunotherapy ethile. Ngaloo ndlela, ixesha kunye nefuthe lemiphumo emibi ayinakucinywa kwisiza esele saziwa ukuba singasebenzisekanga kangangoko kulo hlobo lwesifo somhlaza.
Imizekelo emithathu yomdlavuza womdlavuza onokukunceda ukuxela impendulo yomntu kwi-inhibitors yokuzikhusela i-immune iquka:
- I-PD-L1 ibinzana (nokuba iiseli ngaphakathi kwidumbu libonisa iprotheyini ebizwa ngokuthi i-ligand yokufa-1)
- Umthwalo wentshukumo (nokuba iiseli ngaphakathi kwidumbu ziphethe iqondo eliphezulu lokuguquka kwemfuza)
- Isikhundla sokulungisa isistim (nokuba iiseli ngaphakathi kwimilambo ayifanelekanga ukulungiswa okanye isakhono)
Makhe sihlolisise aba bathathu bendalo ngokubanzi.
Ngale ndlela unako ukuqonda into ethile yesayensi ngenxa yoko kutheni umzimba we-immune system inhibitor ungasebenza kumntu omnye kwaye awunamnye.
I-PD-L1 Inkcazo
I-PDL-1 yiprotheyini echazwe emanzini omzimba wesinye iseli. Injongo yalo kukukhohlisa isistim somzimba ekucingeni ukuba iiseli zomhlaza ziphilile okanye "zilungile." Ngaloo ndlela i-tumor igwema ukuhlaselwa kwe-immune system-i-sneaky, yetystyticated and evasive strategy.
Nangona kunjalo, ngoku kukho izibilini ezivimba iP-L1 . Ngale ndlela umhlaza ufunyanwa ngumzimba womzimba ngenxa yokuba iiseli zomhlaza ziye zalahleka imaski yazo, oko kuthetha. Iziyobisi ezivimbela i-PD-L1 zibizwa ngokuba yi-immune system checkpoint inhibitors kwaye ziquka:
- I-Tecentriq (i-atezolizumab): ibhloko ye-PD-L1
- I-Bavencio (avelumab): ibhloko ye-PD-L1
- Imfinzi (durvalumab): ibhloko ye-PD-L1
Ezi ziyobisi ziye zanceda ekuphatheni unomdla weengqimba ezahlukeneyo ezifana nomhlaza wesisu, umhlaza wesifo somhlaza wamangqamu, kunye nomhlaza wesihlunu se-Merkel.
Kukho kwakhona i-inhibitors yokuzivikela ekukhuseleni ukukhusela i-PD-1 (ebophelela kwi-PD-L1 kwaye inokuboniswa ngamaseli omhlaza), kwaye oku kubandakanya:
- I-Opdivo (nivolumab): ibhloko i-PD-1
- I-Keytruda (pembrolizumab): iibhloko ze-PD-1
Uphando lubonisa ukuba la machiza ancedo ekuphatheni iisomhlaza ezinjengomhlaza we-melanoma, umhlaza wesifo somhlaza wamangqamuzana, umhlaza wengqondo, isifo somhlaza wesisu, isifo somhlaza wesisu kunye nentamo yentamo , kunye neHodgkin lymphoma.
Ekufuneni ama-biomarkers ayeza kubeka ithuba lokuba umntu uphendule kwenye yeziyobisi zingentla, abaphandi baqalise ukuvavanya iiseli zomhlaza ze-PD-L1. Enyanisweni, ngelixa uphando lubonisa ukuthetha kwe-PD-L1 yinto enye enxulumene kakhulu nokuphendula kwi-blocker ye-PD-L1 okanye iP-PD-1, uphando olungakumbi lufuneka luyenze.
Ngamanye amazwi, inkulumo ye-PD-L1 yedwa ayikwazi ukuba ngumqondiso waneleyo wokuba umhlaza womntu uya kunciphisa okanye uphumelele kwenye yezilwanyana ezikhankanywe ngasentla. Akusiyo i-biomarker epheleleyo, kodwa into enhle ngoku.
Umthwalo wokuHlanganisa
Ngaphandle kwegama lakwa-PD-L1 kumaseli omhlaza, abaphandi baye bafunda ukudibanisa phakathi komthwalo wokuguquka komzimba kunye nokuphendula kwayo kwisifo se-inhibitor.
Okokuqala, ukuze uqonde ukuba imithwalo engumngcipheko, kufuneka uqonde ukuba yintoni ukuguqulwa komzimba kunye nendlela oku kuhlobene ngayo nomhlaza.
Yintoni Inguqulelo?
Utshintsho olutshintsho kwi- DNA ngokulandelelana eyenza i-gene. Utshintshi luya kuba yindlalifa (ithetha ukuba idluliselwe ukusuka kubazali bakho) okanye ifunyenwe.
Ngokuguqulwa kwamanzi, ukuguqulwa komzimba kubakho kuphela kwiiseli ze-somatic (zonke iiseli zomzimba, kodwa iqanda kunye neeseli zesisu), ngoko abanako ukudluliselwa kwisizukulwana esilandelayo. Iinguqulelo ezinokuthi zinokuvela kwimimandla engqongileyo, njengobungozi belanga okanye ukutshaya, okanye kwiiphene ezenzekayo xa i-DNA yeseli ikopisha ngokwayo (ebizwa ngokuba yi-replication).
Njengama-cell eqhelekileyo, ukuguqulwa kwamagugu kufumaneka kumaseli omhlaza, kwaye iintlobo ezithile zeekritha zinamazinga aphezulu okutshintshana kunabanye. Ngokomzekelo, iintlobo zomhlaza zomzimba ezimbini ezinomlinganiselo ophezulu wokuguqulwa kwesimo somzimba ngumdlavuza wamaphaphu , ukusuka ekugqibeleni umsi wecuba, kunye ne- melanoma , ukususela kwizuba.
Yithini Umthwalo Ophakamileyo Omkhulu?
Kukho uphando olubonisa ukuba izicubu ezinomlinganiselo ophezulu wokutshintshwa kwe-somatic (umthwalo ophezulu womthamo) zinokuthi ziphendule kwi-inhibitors ye-immune checkpoint kunezicubu ezinezinga elincinci lokuguquka kwemfuyo.
Oku kunengqiqo kuba, ngokuguquguquka okungakumbi, i-tumor yayiza kuba yinto ebonakalayo ngakumbi kwi-system's immune system. Ngamanye amazwi, kunzima ukufihla kunye nazo zonke ezo zimizo zokungafani.
Enyanisweni, oku kulandelwa kwemizimba emitsha kugqiba ukudala ii-proteins ezithintekayo ezibizwa ngokuba yi-neoantigens. Zizo zi-neoantigens ezithemba ukuba ziyamkelwa ngumzimba wokuzikhusela kwaye zihlaselwa (ezibizwa ngokuba ngumhlaza we-immunogenic neoantigens kuba zivuselela iimpendulo zamagciwane).
Isimo sokuLungisa ukuThatyathwa
Umzimba womntu uhamba ngendlela yokulungisa rhoqo ukulungisa iziphene ze-DNA ezenziwe ngexesha lokuphindaphinda kweseli. Le nkqubo yokulungisa iiphene ze-DNA ibizwa ngokuthi ukulungiswa okungafaniyo.
Uphando olwenziwe kwi-inhibitors lokuhlola i-immune luye lwabonisa ukuba imeko yokulungisa i-tumor ingasetyenziselwa ukuxela impendulo yomntu kwi-immunotherapy. Ngokukodwa, izicubu ezingenakulungiswa ukulungisa ukulungiswa (oko kuthetha ukuba zombini iikopi zokulungiswa kwezinto eziphathekayo ezingaguqukanga okanye zithulisiwe) azikwazi ukulungisa iimpazamo zeDNA.
Ukuba umhlaza wamaseli unciphise amandla okulungisa umonakalo we-DNA, unokuqokelela ukuguquka kwezinto ezininzi ezenza ukuba ziboneleleke kwi- immune system . Ngamanye amagama, baqala ukukhangela ngokubanzi nangaphezulu kwiiseli eziqhelekileyo (ezingenakuncinci).
Uphando lubonisa ukuba iintsholongwane ezinokuphulukana okungahambi kakuhle ziqulethe iiseli zegazi ezimhlophe ezishiye igazi kwi-tumor-uphawu lompembelelo olukhuselekileyo lwe-immune kunye nomqondiso wokuthi lo mhlaza usengozini enkulu yokukhusela i-immunotherapy.
Oku kuhambelaniswe nokulungiswa okungafaniyo-ukulungisa i-cancer ye-skilled, ngokubonisa ukungena kwe-white cell tumor infiltration.
I-Cancer kunye neNkqubo ye-Immune System: Intsebenziswano yeComplex
Ukuvela kwama-immunotherapi ekujoliswe kuyo ekujoliswe kuyo iiprotheni ziye zazisa uvuyo kunye nethemba kwabo baphatha kwaye banomdlavuza. Kodwa ngokunikezelwa kwe-biomarker engaphelele ye-PD-L1 ibonakaliso, amanye ama-biomarkers athembekileyo kufuneka achongwe kwaye aphenywe. Nangona ukulayishwa komthwalo kunye no-DNA ukulungiswa okungaqhelekanga kuqale, iimvavanyo zisadingeka ziqinisekiswe ukuba zisetyenziswe kwizigulane.
Ngaloo ndlela, ukufumana ithuba lomntu lokuphendula kwisifo esithile sempilo kungasuka kuhlalutyo lweentlobo ezininzi zeenkcukacha-iprofile yezofuzo, ngoko kuthetha.
ILizwi
Kwinqaku lokugqibela, kubalulekile ukuba ungabikho phantsi kweenkcukacha eziyinkimbinkaliso apha.
Kunoko, nceda uqonde ukuba ngelixa uthembisa kwaye unomdla kakhulu, i-inhibitors ye-immune check-in kuphela ivunyiwe yi-FDA ukuphatha iintlobo ezithile kunye nezigaba zomhlaza. Ingaba okanye ayiyi kuba yimpendulo kuwe okanye othandekayo kodwa ubonise inkqubela phambili ekuphuhliseni unyango olutsha lomhlaza. Ngayiphi na indlela, hlalani nethemba uze uqhubeke nohambo lwakho oluxhasayo.
> Imithombo:
> Farkona S, i-Diamandis EP, i-Blasutig IM. I-cancer immunotherapy: ukuqala kokuphela komhlaza? BMC Med . 2016 Meyi 5; 14: 73.
> Le Dt et al. I-PD-1 ikhuselekile kwiimvumi kunye nokulahleka okungahambi kakuhle. N Eng J Med . 2015 Juni 25; 372 (26): 2509-20.
> Masucci GV et al. Ukuqinisekiswa kwezilwanyana eziqingqiweyo ukuxela impendulo kwi-immunotherapy emdlalweni: Umqulu 1 - ukuqinisekiswa kwangaphambili nokuhlalutya. J Omnye umdlavuza . 2016 Novemba 15; 4: 76. eCollection 2016.
> Mouw KW, Goldberg MS, Konstantinopoulos PA, D'Andrea AD. Umonakalo we-DNA kunye nokulungiswa kwezixhobo zokuphendula nge-immunotherapy. Cancer Discov . 2017 Julayi; 7 (7): 675-93.
> Shoushtari AN, uWolchok J, uHolman M. (2017). Imigaqo yomhlaza we-immunotherapy. Atkins MB, ed. Isemgangathweno. Waltham, MA: UpToDate Inc.