Ngaba bekungeke kube kuhle ukuba oogqirha banokukhangela umdlavuza wakho, jonga kwiindlela ezahlukeneyo zokwelapha ezikhulayo, kwaye wenze isigqibo malunga naluphi ukhetho olunokuphumelela?
Nangona i-oncologists inokuthi, kumaxesha amaninzi, inezixhobo ezifanelekileyo kunye nedatha yokuhlenga nokuthelekisa unyango oluthile, olutsha olusandul 'ulwabiwo lunokuthi kunzima kunzima ukuqikelela, ngokungabikho kwamava.
Ukuphucula ulwazi kuvela kwiimvavanyo zeclini, apho izigulane zivuma ukufaka izifundo kunye neziyobisi zophando ezibonise isithembiso; kodwa, njengoko igama elithi 'ityala' libhekisela, kukho iqondo lokungaqiniseki malunga nokuba isilwanyana siya kwenza njani kwaye ngubani oza kunceda kakhulu-oko kukuthi, zeziphi iintlobo zesigulane kunye neentlobo zesifo somhlaza.
Yintoni i-Cancer Immunotherapy?
I-cancer immunotherapy yonyango olubandakanya iindawo ezithile zesistim somzimba somntu ukulwa nesifo esibulalayo. Omnye umzekelo we-immunotherapy usetyenziso lwee- antibodies ezifana ne-rituximab kunye ne-obinutuzumab . Ama-antibodies e-Monoclonal ayenziwa ngabantu, okanye ama-proteins system. Ezi zikhuselo ziyakwazi ukuhlasela isahlulo esithile sentsholongwane yomhlaza kwinto eyaziwa ngokuba yonyango olujoliswe kuyo .
Ezinye iintlobo ze-immunotherapy zengculazi zibandakanya i- inhibitors yokuhlola i-immune , ezithatha 'iibhuleki' kwisistim somzimba sokuzivikela ekuncedeni ukuqaphela nokuhlasela iiseli zomhlaza.
Ihlabathi le-immunotherapy le-cancer alinakucinganiswa nale mizekelo ingentla, nangona kunjalo, kunye neembono ezintsha zokusebenzisa umzimba wakho womzimba ukulwa namaseli omhlaza uyaqhubeka nokuphuculwa.
Ngaba i-Immunotherapy isebenza kuzo zonke i-Cancer?
Umntu ngamnye uhlukile, nomhlaza womntu ngamnye uhlukile; akuyena wonke umntu ophendula ngendlela efanayo kwi-immunotherapy efanayo.
Ukulinganisa ngokuchanekileyo, kwangaphambili, apho abantu banokuthi baphendule kwi-immunotherapy kuya kuba luncedo kwiindawo ezininzi. Kwisigulane, ingasindisa ixesha elibalulekileyo, elinokuthi liguqulele kwisibonelelo sonyango.
Ngamanye amagama, awuyi kuchitha ixesha lakho okanye iziphumo ezichaphazela umngcipheko uzama into enokuthi ibe nempembelelo encinci xa kunokuthi kubekho 'isibhamu esikhulu' okanye unyango olungakumbi olukhoyo. Kodwa umntu angazi njani olu hlobo lento ngaphambili? Elinye ibali eliphathelele indlela abacwaningi be-oncologists kunye nomdlavuza abaye benza ngayo oku kuqala ngento ethiwa neoantigens.
I-Neoantigens: I-Achilles I-Helic Heal?
Iiseli zeCans can be sneaky. Zivame ukuba neenguqu ezininzi kwiijisi zazo, ezinye zazo zihambelana nokukwazi kwabo ukwenza izinto eziqhelekileyo, iiseli ezinempilo azikwazi. Ezinye zeenguqu zenzeke ngokwahlukileyo ngokomzimba okanye ngaphandle kweeseli zomhlaza ezingabonwa ngumzimba womzimba. Ezi nxalenye zomzimba weeseli zomzimba ezikwazi ukuwabona njengamazwe angaphandle abizwa ngokuthi "neoantigens."
I-Neo, ithetha intsha, kuba ivela esandula kwiiseli zethu, isuke ihlaselwe ngumhlaza , ngokuchasene nama-antigens aqhelekileyo asoloko ethetha ngezifo ezithathelwanayo, umzekelo.
Ama-antigens rhoqo angafumaneka ngaphandle kweebhaktheriya, okanye iiseli ezithelelekileyo zentsholongwane. Ngokwahlukileyo, i-neoantigens ifana neeflegi ezibomvu ezingabonakalisa isistim somzimba sokuthi iiseli zethu zizenza kakubi.
I-Neoantigens ikhokelela ekusebenziseni amaseli egazi ezimhlophe aziwa njengeT-seli -amasosha omzimba omzimba. La majoni aseT-cell ahamba ngeemitha zegazi, njengendlela ye-cobblestone yaseRoma yakudala, ukufikelela kwisiza seeseli ezingekho emthethweni, zingenayo i-tumor kwaye zancedise ukuhlalisa abantu basekuhlaleni beeseli ezibulalayo.
Ngoko, i-neoantigens yenye yezona zihluthulelo zonyango lokulwa nomhlaza olususelwa kumzimba.
Oko kwathiwa, ukunqoba imfazwe kungekho nto ibandakanya ukuxilongwa kwe-immunotherapy yedwa, kwaye kufuneka kusetshenziswe indlela yokutya yomhlaba. i-immunotherapy isetyenziswa rhoqo ngokubambisana ne-cytotoxic chemotherapy kunye / okanye nezinye i-immunotherpies, kuxhomekeke kwisifo esibi kunye nesigulane ngasinye .
Ngaba I-Immunotherapy Iyasebenza Kwam?
Lo ngumbuzo obalulekileyo kwi-oncology yanamhlanje, kunye nomnye osebenza ngokusebenzayo. Kuloo sukelo, iziganeko ezimbini zeeseli zomhlaza wakho zinokunceda oogqirha baxelele ukuba i-immunotherapi ekhoyo iya kusebenza njani: TMB kunye neMSI.
Ukuxhamla umthwalo wokunyakaza, okanye i- TMB , kunokucingelwa njengoluhlu lwazo zonke iinguqu kwiijethi kumaseli omhlaza ayenayo i-gry-genes, ngokomzekelo, esetyenziswe kwikhowudi yazo zonke izinto eziqhelekileyo iseli efuna-kodwa utshintsho okanye utshintsho kwiimeko zeeseli zomhlaza. I-TMB ngamanye amaxesha ikwabizwa ngokuba ngumthwalo opheleleyo womthwalo okanye umthwalo wokutshintsha.
Izibilini eziphezulu ze-TMB zikholelwa ukuba zinama-neoantigens amaninzi kwaye ngoko iphendule bhetele kwi-immunotherapy. Iiseli zomhlaza zingaphelela nge-TMB ephezulu ngokudityaniswa komhlaza, kuquka ucuba okanye ukukhanya kwe-UV. Enye indlela ngokungazinzi kwe-microsatellite, okanye i- MSI , eli gama lobuchwepheshe elibhekiselele kwingxaki ngemizimba yendalo yakho yokulungiswa kwe-DNA-ingxaki ephumela ekutshintsheni kakhulu nokungahambisani nobude bokuphindaphinda i-DNA gene gene.
Enye inkampani ebizwa ngokuba yi-Foundation Medicine ngoku inikeza uvavanyo lokuqala oluhlanganisiweyo ngokupheleleyo, oluqinisekisiweyo lwe-TMB njengenxalenye yesilingo sawo se-FoundationOne, esinokukunceda ukuqikelela indlela umntu angayiphendula ngayo kwi-immunotherapy.
"I-genomes ephosakeleyo yinto eqhelekileyo yazo zonke i-cancer," kuchaza uVincent Miller, MD, igosa eliphezulu lezonyango kwi-Foundation Medicine. "Ukuxhamla kunye nenani eliphezulu kakhulu lokuguqulwa kwamanzi kunokwenzeka ukuba kuvelise iiprotheni ezingenasimo ezibizwa ngokuthi i-neoantigens. Isistim somzimba siyaziqonda ezi zizwe zingaphandle kwaye zihamba ziqaphile, ziqalise uchungechunge olunzima lwamaqhinga okuhlasela isifo. "
Ngaba i-Inhibitor yoVimba yoMzimba iya kuSebenza kum?
Isalathisi siqinisa ukuba ezinye iintsholongwane zenze iindlela ezihlambulukileyo zokukhusela isistim somzimba-ngokwenza amaprotheni okwenene acacise ezinye iintlobo zamaseli omzimba wakho omzimba. Isixhobo sokugaya i-biologic , ukuba uthanda.
Ukuthintela umhlaza ukuba uzigqoke ngale ndlela, ezinye i-immunotherapi zenzelwe ukuvimba ezi protein zokukhusela umzimba. Ezi zi-immunotherapi, ezibizwa ngokuba yi- immune checkpoint inhibitors , ziquka ezo zibizwa ngokuba yi- anti-PD1 kunye ne-anti-PDL1 . Kwaye, njengokuba kukho nezinye iintlobo ze-immunotherapy, kukho ubungqina obubonisa ukuba amazinga aphezulu angama-neoantigens kumaseli omhlaza anxulumene neempendulo ezingcono kwi-inhibitors ye-immune checkpoint.
Impendulo ukujonga i-inhibitors yendawo ihluka ukusuka kuma-20 ekhulwini kumdlavuza wamaphaphu ukuya kuma-80 ekhulwini eHodgkin lymphoma. Isizathu sokuba kutheni izilwanyana ezithile ziphendule kwi-inhibitors yokujonga kunye nabanye abantu akucaci.
Kubaluleka kokubikezela ukuphendula ngekliniki
Ezi zixhobo zokuqikelela kunye nempumelelo yazo ziyinhloko yengxoxo kwintlanganiso yalo nyaka we-American Society of Clinical Oncology, okanye i-ASCO.
I-TMB ibonisiwe ukuba ibonelele amathuba amakhulu okuphendula kunye nobude obude beempendulo zomhlaza we-immunotherapi kwizigulane ezineomhlaza wesisu, umhlaza womphunga, i-melanoma kunye nezinye i-cancer eziphambili. Ukongeza kwiTMB, i-FoundationOne iphinda ilinganise ukungazinzi kwe-microsatellite, emele uvavanyo olulodwa ukukhokela izigqibo zonyango kwiimvavanyo ezijoliswe kuzo, izilingo zeklinikhi kunye ne-FDA-evumelweyo yomhlaza we-immunotherapies usebenzisa i-biopsy eyodwa.
"I-Cancer immunotherapi ihamba phambili kwonyango lomhlaza, kwaye iindlela ezintsha, iindlela ezininzi zifunekayo ukuxela izimpendulo zekliniki kule nto ebalulekileyo, kodwa nexabiso elibizayo, iklasi yezonyango," kutsho uDkt. Miller.
"Ukukwazi ukulinganisa ngokuchanekileyo i-biomarker ngexesha elifanayo, kubandakanywa ne-TMB kunye ne-MSI, kubaluleke kakhulu kwintsimi yomhlaza we-immunotherapy, kunye neyodwa kwi-Medicine Foundation," utshilo u-Thomas George, MD, umlawuli weprogram ye-oncology, iYunivesithi yaseFlorida. . Ukuhlanganiswa kweMicrosoft Foundation yamaphulo okulandelelanisa okuphambili kunye ne-algorithm ecacileyo kakhulu ininika ilungelo lokufikelela kuzo zonke izigulane ze-genomic ezifanelekileyo kwizigulane zam kanye kanye, ukunceda ukugcina ixesha kunye nezicubu. "
"Sakhuthazwa yiziphumo ezenziwe kwi-ASCO, kubandakanywa nokukwazi ukuchonga izigulane ezinokuthi zizuze kwi-inhibitor immunotherapy," kutsho uDkt. Miller. "Injongo yethu kukuxhobisa oogqirha kunye nezigulane ezineenkcukacha ezifanelekileyo ezifanelekileyo, ezinokuthi zenze i-geneomic information, kwaye sivuyiswe ukunikela isisombululo sethu esicacileyo sokulinganisa iTMB kunye neMSI kanye kunye nokuchaneka okuthe ngqo, kuxhaswe ngolu hlobo oluchanekileyo kunye nokugxilwa kwimiba yokuqonda ukusuka kwisiseko sethu solwazi FoundationCORE. Le nto ayikho enye inxaxheba yokunikezela ngokulandelana kwesizukulwana esilandelayo. "
I-Independent ye-FoundationOne kunye ne-FoundationOne i-Heme, i-Foundation Medicine inikezela uvavanyo lwe-PD-1 kunye ne-PD-L1 yeprotein ye-protein, ukubonelela, ngokudibanisa neesisayiti ze-FoundationOne, isistim esipheleleyo sesifo se-immunotherapy ze-oncologists.
ILizwi
Ngoxa le nto iyindawo ethembisayo, inzululwazi isakhulayo kwaye iimvavanyo ezahlukahlukeneyo zisacingwa kwaye ziqinisekisiwe. Zonke izixhobo ezikhoyo ezikhoyo zamanje zokubikezela impendulo yeklinikhi ukujonga i-inhibitors yendawo iphando kuphela kwaye akukho mvavanyo ephunyeziweyo ye-FDA ekwazi ukuqikelela ngokuchanekileyo impendulo yokujonga i-inhibitors.
> Imithombo:
> I-Medicine yeSiseko iveza idatha entsha kwi-ASCO 2016 ibonisa ukuba i-FoundationOne inokukunceda ukuqikelela ukuphendula komdlavuza we-immunotherapy kuzo zonke iindidi ezinomdlavuza.
Ansell SM, Lesokhin AM, Borrello I, et al. I-PD-1 i-Blockade kunye neNivolumab ekubuyiselweni kwakhona okanye kwi-Lymphoma ye-Refractory. N Engl J Med. 2015; 372 (4): 311-319.
Pardoll DM. Ukukhutshwa kweengcambu zokuzikhusela kumzimba kumhlaza we-immunotherapy. Nat Rev Cancer. 2012; 12 (4): 252-64.