Ukuhlola ama-Biomarkers Okungahle Abikezele Ukuthi I-Cancer Yakho Ihlehla
Umqondo wokusebenzisa amasosha omzimba omuntu ukulwa nomdlavuza akuyona inkaba, kodwa ukuthola lo mqondo ukuhumusha emisebenzini yezokwelapha bekulokhu impi ekukhuphukeni.
Izindaba ezinhle ukuthi ngokuphumelela kwamuva kwezidakamizwa okuthiwa i- immune checkpoint inhibitors , ukusetshenziswa kwe-immunotherapy yokwelapha umdlavuza kuye kwavuselelwa. Manje, ngaphezu kokuthuthukisa ama-inhibitors amaningi omzimba wokuzivikela omzimba, abacwaningi bathola izindlela zokubona kangcono ukhetho olungcono lwalezi zidakamizwa.
Ngamanye amazwi, ochwepheshe bafuna ukuqoqa ndawonye ukuthi iziphi iziguli ezingase zizuze kuloluhlobo lwe-immunotherapy, okusho ukuthi umdlavuza wabo ungase uphephe noma uphelelwe kanjani ngenxa yalokhu ukwelashwa.
Izimpendulo aziqondile, ngakho-ke kufanelekile ukuthatha isikhathi sokuqonda okuyisisekelo salolu cwaningo oluqhubekayo.
Impendulo ye-Immune Checkpoint Blockade: Ama-Biomarkers
Abacwaningi baphenya izindlela zokubona ukuthi yiziphi izimpawu zokuzivikela ezizophumelela kakhulu kwisiguli ngasinye. Okungcono, i-oncologist (udokotela onomsebenzi wokwelapha umdlavuza) angathanda ukuhlola amangqamuzana omdlavuza womuntu we-biomarker (noma ama-biomarker amaningi).
Lezi zimpawu zizobikezela ukuthi kungenzeka yini umuntu ukuthi aphendule emzimbeni othile. Ngale ndlela, isikhathi kanye namathuba okuba nemiphumela emibi awachitheki emthini owaziwa ukuthi awusebenzeli kangako kulolo hlobo lomdlavuza weselula.
Izibonelo ezintathu zomdlavuza womdlavuza ezingasiza ukubikezela impendulo yomuntu kuma-inhibitors wokuzivikela nge-immune zihlanganisa:
- Inkulumo ye-PD-L1 (kungakhathaliseki ukuthi amangqamuzana angaphakathi kwesisu aveza iphrotheni ebizwa ngokuthi i-ligand-death ligand 1)
- Umthwalo wokunyakaza (kungakhathaliseki ukuthi amangqamuzana angaphakathi kwesisu aphethe izinga eliphezulu lokushintshashintsha kwezakhi zofuzo)
- Isimo sokulungisa esimweni (kungakhathaliseki ukuthi amangqamuzana angaphakathi kwesikhumba ayifaneleki ukulungiswa noma ukuqeqeshwa)
Ake sihlole lezi zici ezintathu ngokuningiliziwe.
Ngale ndlela ungakwazi ukuqonda kancane isayensi ngenxa yokuthi isimiso sokuzivikela sokuzivikela komzimba singasebenza kumuntu oyedwa hhayi esinye.
I-PD-L1 Incazelo
I-PDL-1 iyiprotheni evezwe phezu kwamanye amangqamuzana omdlavuza. Inhloso yalo ukukhohlisa isimiso somzimba sokuzivikela ekucabangeni ukuthi amangqamuzana omdlavuza aphilile noma "ahle." Ngale ndlela i-tumor igwema ukuhlaselwa kwesistimu yomzimba-isisindo esiyinkimbinkimbi, kodwa esiyinkimbinkimbi futhi esiphuthumayo.
Kodwa-ke, kukhona manje izidakamizwa ezivimbela i-PD-L1 . Ngale ndlela umdlavuza utholakala amasosha omzimba ngoba amangqamuzana omdlavuza alahlekelwe imaski yawo, okushoyo. Izidakamizwa ezivimbela i-PD-L1 zibizwa nge-inhibitors yokuhlola amasosha omzimba futhi zifaka:
- I-Tecentriq (atezolizumab): ivimbela i-PD-L1
- I-Bavencio (avelumab): ivimbela i-PD-L1
- I-Imfinzi (durvalumab): ibimbela i-PD-L1
Lezi zidakamizwa ziye zasiza ekwelapheni amakhemikhali ahlukahlukene afana nomdlavuza wesibeletho, umdlavuza ongasona omncane wesifo samaphaphu, nomdlavuza wesikhumba seMelkel.
Kukhona futhi ama-inhibitor okuhlola omzimba okuvimbela i-PD-1 (okubophezela ku-PD-L1 futhi angabonakaliswa ngamaseli omdlavuza), futhi lokhu kufaka:
- I-Opdivo (nivolumab): ivimbela i-PD-1
- I-Keytruda (pembrolizumab): ivimbela i-PD-1
Ucwaningo lubonisa ukuthi lezi zidakamizwa ziwusizo ekwelapheni i-khansa efana ne-melanoma, umdlavuza ongasona omncane wamaphaphu, umdlavuza wezinso, umdlavuza wesisu, ikhanda lekhanda , ne-Hodgkin lymphoma.
Ekufuneni ama-biomarkers angase anqume amathuba okuba umuntu aphendule kwenye yezidakamizwa ezingenhla, abacwaningi sebeqale ukuhlola amangqamuzana omdlavuza we-PD-L1. Ngempela, kuyilapho ucwaningo lubonisa ukukhulunywa kwe-PD-L1 yisici esisodwa esithintana kakhulu nokuphendula ku-blocker ye-PD-L1 noma i-PD-1, ucwaningo olwengeziwe luzodinga ukwenziwa.
Ngamanye amazwi, inkulumo ye-PD-L1 yedwa ingase ingabi isibonakaliso esanele sokuthi umdlavuza womuntu uzohlehlisa yini noma uchithe ngesinye sezidakamizwa okukhulunywe ngenhla. Akuyona i-biomarker ephelele, kodwa into enhle kuze kube manje.
Umthwalo Wokunyakaza
Ngaphandle kwenkulumo ye-PD-L1 emangqamuzaneni omdlavuza, abacwaningi baye bahlola ukuxhumana phakathi komthwalo wokuguquka komzimba nokuphendula kwayo ekuvikelweni kwe-immune checkpoint inhibitor.
Okokuqala, ukuze uqonde ukuthi imithwalo yokuguquguquka ingakanani, kufanele uqonde ukuthi ukuguqulwa komzimba nokuthi lokhu kuhlobene nomdlavuza.
Kuyini Ukuguquka?
Ukuguqulwa kwenguquko ku- DNA ukulandelana okwenza isakhi. Izinguquko zingaba yifa (okusho ukuthi zidluliselwe kubazali bakho) noma zitholakale.
Ngezinguquko ezitholakalayo, ukuguqulwa komzimba kuvele kumaseli angama-somatic (wonke amangqamuzana emzimbeni, kodwa amaqanda namasamu omzimba), ngakho angeke adluliselwe esizukulwaneni esilandelayo. Izinguquko ezithintekayo zingase zenzeke ezimweni zemvelo, njengokulimala kwelanga noma ukubhema, noma kusuka ephutha elenzeka lapho i-DNA yeselula ikopisha ngokwayo (ebizwa ngokuthi ukuphindaphindiwe).
Njengamaseli avamile, ukuguqulwa kwezinto ezitholakalayo kuyenzeka futhi emangqamuzaneni omdlavuza, kanti izinhlobo ezithile zamanomdlavuza zinamanani aphezulu okuguquka kwesinye. Ngokwesibonelo, izinhlobo ezimbili zomdlavuza ezinomqondo ophezulu wezinguquko ezishintsha umxhwele yi- cancer yomaphaphu , kusukela ekubhekaneni nentuthu kagwayi, ne- melanoma , kusukela ekukhanyeni elangeni.
Uyini Umthwalo Omkhulu Wokuguqula?
Kukhona ucwaningo olubonisa ukuthi izicubu ezinamazinga aphezulu okuguquguquka komzimba (ukuphakama okukhulu komzimba) kungenzeka ukuthi ziphendule kuma-inhibitors wokuhlola okuzivikela emzimbeni kunama-tumors anezinga eliphansi lokushintshashintsha kwezakhi zofuzo.
Lokhu kunengqondo ngoba, ngokuguquguquka okungaphezulu, isisu singase sibheke ngokwengeziwe esimisweni somzimba somuntu. Ngamanye amazwi, kunzima ukufihla kuzo zonke lezozinto ezilandelanayo zofuzo.
Eqinisweni, lokhu kulandelwa kwezakhi zofuzo kuphelela ukwakha amaprotheni amasha aqondene ne-tumor okuthiwa i-neoantigens. Yilezi zingu-neoantigens ezithandwa ngethemba lokuzivikela omzimba futhi zihlaselwa (okuthiwa umdlavuza we-immunogenic neoantigens ngoba zivusa ukuphendula komzimba).
Isimo sokuPhathwa kweMismatch
Umzimba womuntu udlula inqubo yokulungisa njalo yokulungisa amaphutha e-DNA okwenziwa ngesikhathi sokuphindaphinda kweseli. Le nqubo yokulungisa amaphutha e-DNA ibizwa ngokuthi ukulungiswa okungalungile.
Ucwaningo olwenziwe nge-immune checkpoint inhibitors luye lwaveza ukuthi isimo sokulungisa okungenakulinganiswa kwesisu singasetshenziselwa ukubikezela impendulo yomuntu ku-immunotherapy. Ngokuqondile, izicubu ezingenakulinganiswa ukulungiswa kwempahla (okusho ukuthi kokubili amakhophi wokugaya okungaqondakali aguqulwe noma athuliwe) akwazi ukulungisa amaphutha e-DNA.
Uma umdlavuza wegazi unciphise ikhono lokulungisa umonakalo we-DNA, angakwazi ukuqoqa izinguquko eziningi ezenza zibonwe esimisweni somzimba sokuzivikela . Ngamanye amazwi, baqala ukubheka ngokungafani nakakhulu namaseli avamile (angenangqangi).
Ukucwaninga kubonisa ukuthi ukwelashwa okungahle kwenzeke ngokulungisa okungenakulinganiswa kuqukethe amangqamuzana amaningi amhlophe egazi asele egazini ukuze afake isisu-isibonakaliso sempendulo enamandla yegciwane lesandulela ngculazi kanye nesibonakaliso sokuthi lo mdlavuza usengozini enkulu yokuzivikela.
Lokhu kuqhathaniswa nokusabalalisa-ukulungisa amakhemikhali anempilo, ngokubonisa ukungena kwegazi elimhlophe elimhlophe.
I-Cancer ne-Immune System: Ukusebenzisana Kokuncintisana
Ukuvela kwama-immunotherapies okuhloswe ngawo amaprotheni okubhekisisa kuye kwaletha injabulo nethemba kulabo abaphatha imithi yomdlavuza futhi bahlala njalo. Kodwa uma kunikezwa i-biomarker engaphelele ye-PD-L1 inkulumo, amanye ama-biomarkers athembekile adinga ukukhonjwa nokuphenywa. Ngenkathi ukulayishwa komzimba kanye nokulungisa okuyi-DNA kuqala kahle, ukuhlolwa kudingeke kuqinisekiswe ukusetshenziswa kweziguli.
Ngalokho, ukukhetha ithuba lomuntu lokuphendula ku-immunotherapy ethile kuzotholakala ngokuhlaziywa kwezinhlobo eziningi zedatha-iphrofayli yezakhi zofuzo, okushoyo.
Izwi elivela
Ngombhalo wokugcina, kubalulekile ukuthi ungatholakali kakhulu ngemininingwane eyinkimbinkimbi evezwe lapha.
Kunalokho, sicela uqonde ukuthi nakuba uthembise futhi uthakazelisa kakhulu, ama-inhibitors okuhlola i-immune yi-FDA kuphela evunyelwe ukuphatha izinhlobo ezithile nezigaba zomdlavuza. Kungenzeka noma kungabi yimpendulo kuwe noma othandekayo kodwa kubonise intuthuko enkulu ekuthuthukiseni ukwelashwa okusha ngomdlavuza. Noma iyiphi indlela, hlala ushemba futhi uqhubeke nohambo lwakho oluqinile.
> Imithombo:
> Farkona S, Diamandis EP, i-Blametig IM. I-cancer immunotherapy: ukuqala kokuphela komdlavuza? BMC Med . 2016 Meyi 5; 14: 73.
> Le Dt et al. I-PD-1 ivinjelwe emathunjini ngokuntuleka kokulungisa okungalungile. N Eng J Med . 2015 Jun 25; 372 (26): 2509-20.
> Masucci GV et al. Ukuqinisekiswa kwezinto eziphilayo ukubikezela ukusabela ekuzivikelweni kwe-immunotherapy emdlalweni: Umqulu 1 - ukuqinisekiswa kwangaphambi kokuhlaziya nokuhlaziya. J Ngomunye Umdlavuza . 2016 Nov 15; 4: 76. eCollection 2016.
> Mouw KW, Goldberg MS, Konstantinopoulos PA, D'Andrea AD. Ukulimala kwe-DNA nokulungisa izidakamizwa ze-immunotherapy response. I-Cancer Discov . 2017 Jul; 7 (7): 675-93.
> Shoushtari AN, Wolchok J, Hellman M. (2017). Izimiso zomdlavuza we-immunotherapy. I-Atkins MB, ed. Kusesikhathini. Waltham, MA: UpToDate Inc.