I-Ultrasensitive liquid biopsy iziveza njengenye yamathuluzi athembisayo kakhulu okuqonda, cishe ngesikhathi sangempela, ukuthi izimila zisabela kanjani ekwelashweni nge-immunotherapy. Kusukela kusampula yegazi elula, amaqembu ocwaningo angalandelela izigxivizo zeminwe zama-molecule zomdlavuza futhi abikezele ukuthi ukwelashwa kuyasebenza noma ukuthi isu lidinga ukubuyekezwa.
ESpain, i -Vall d'Hebron Institute of Oncology (VHIO) ihola iphrojekthi enkulu ekhombisa ukuthi ukuhlaziywa okunembile kakhulu kwe-DNA yesimila esijikelezayo (ctDNA) kungabikezela kusenesikhathi impendulo, ukusinda, kanye nokuqhubeka kwezimila ezigulini ezinomdlavuza othuthukisiwe ophathwe nge-immunotherapy ezivivinyweni zemitholampilo zesigaba 1. Okutholakele kukhomba ushintsho olukhulu endleleni iziguli zomdlavuza ezikhethwa futhi ziqashwe ngayo.
Kuyini i-ultrasensitive liquid biopsy futhi kungani kubalulekile ekwelashweni nge-immunotherapy?
Ukwelashwa nge-immunotherapy kushintshe indlela yokwelapha umdlavuza ngokusebenzisa isimiso somzimba sokuzivikela sesiguli ukuze sihlasele amangqamuzana esimila. Kodwa-ke, ukusebenza kwayo kusekuncane: cishe yi-10-20% yeziguli ezithola izimpendulo ezihlala isikhathi eside, okugqamisa isidingo sama-biomarker athembekile ukuze kutholakale kangcono ukuthi ubani ongazuza ngempela kulezi zindlela zokwelapha.
Kulo mongo, i-liquid biopsy isekelwe ekutholakaleni kwezingcezu ze-DNA egazini ezikhishwa yizimila , ezaziwa ngokuthi i-circulating tumor DNA. Njengoba kuyindlela engahlaseli, ivumela ukusampula okulandelanayo ngaphambi kokuqala ukwelashwa nge-immunotherapy kanye nakulo lonke ukwelashwa, okuvumela ukuqapha ukuvela kwesimila ngaphandle kwesidingo se-biopsies yezicubu eziqhubekayo noma amasu okuthwebula izithombe ahlaseli kakhulu.
Ithimba le-VHIO lithathe le ndlela isinyathelo esiqhubekayo ngeplatifomu yokuhlaziya i-ctDNA ezwela kakhulu ekwazi ukubona izinguquko ezincane kakhulu enanini kanye namaphethini ama-molecule ale DNA yesimila ku-plasma. Lokhu kunemba okwengeziwe kwenza kube nokwenzeka ukuhlanganisa i-ctDNA dynamics nokusabela noma ukumelana ne-immunotherapy ezinhlobonhlobo zezinhlobo zomdlavuza.
Njengoba iqembu locwaningo lichaza, lobu buchwepheshe bubavumela ukuthi "balinganise umunwe we-molecule womdlavuza" egazini futhi "bawulandelele" ngokuhamba kwesikhathi , banikeze umbono onemininingwane eminingi ngalokho okwenzekayo esigaxeni kunokuhlolwa kwezithombe kuphela. Ngale ndlela, i-biopsy yoketshezi ebucayi kakhulu ivela njengesengezo esinamandla, futhi kwezinye izimo kungenzeka ukuthi ithathe indawo yamasu endabuko e-radiological ekuqapheni impendulo yokwelashwa.
Ucwaningo olunezibonelo ezingaphezu kuka-1.500 ezivela ezigulini ezinomdlavuza osezingeni eliphezulu
Umsebenzi oholwa yi- VHIO wenziwa ngaphakathi kohlaka lwezivivinyo zemitholampilo zesigaba soku-1 neziguli ezihlushwa yizimila ezisakazeka kalula —okungukuthi, umdlavuza osuthuthukile osuyeke ukusabela ekwelashweni kwangaphambilini. Lena yinhlangano eyinkimbinkimbi kakhulu, lapho ukuba namathuluzi avumela ukulungiswa okunembile kwe-immunotherapy kubalulekile.
Eqenjini eliyinhloko, amasampula egazi angu-1.455 ahlaziywa isikhathi eside ezigulini ezingu-136 ezinezinhlobo zomdlavuza ezingu-24 ezahlukene (kufaka phakathi izimila ezivamile ezifana nomdlavuza we-colorectal ), zonke ezelashwa ngemigqa eyodwa kuya kwemithathu ye-immunotherapy ezivivinyweni zesigaba sokuqala. Ngokusekelwe kulolu lwazi, ithimba lihlole ukuthi amazinga namaphethini e-cytotoxic T-DNA ashintsha kanjani kulo lonke ukwelashwa futhi lawaqhathanisa nokuvela kwemitholampilo kanye nemisebe ye-radiological yecala ngalinye.
Ukuze kuqiniswe ukuqina kwemiphumela, okutholakele kuleli qembu elibheka emuva kwaqinisekiswa kamuva eqenjini lesibili leziguli ezingu-66 , nazo ezelashwa nge-immunotherapy. Le ndlela ekabili, kokubili ebheka emuva kanye neyangaphambi kwesikhathi, ikhulisa ukuzethemba kokuthi ubudlelwano obubonakalayo phakathi kwe-ctDNA kanye nempendulo yokwelashwa akubangelwa yingozi.
Lolu cwaningo luyingxenye yesikhulumi sephrojekthi ye -IMMUNOMICS-VHIO , esihlanganiswe nohlelo lwe-VHIO lwe-Comprehensive Cancer Immunotherapy and Immunology Program (CAIMI) futhi sisekelwa yi-BBVA Foundation. Ngaphezu kwalokho, ilabhorethri kaRodrigo Toledo ithola uxhaso oluvela kwi-FERO Foundation futhi isebenzisana nephrojekthi ye-PREDICT, kanti umsebenzi uyingxenye yezinhlangano zaseYurophu ezifana ne -DART kanye ne-UpSMART Accelerator , eyokugcina isekelwa yi-Spanish Association Against Cancer.
Ukujikeleza i-DNA yesimila njenge-biomarker yokusabela nokusinda
Enye yezinto ezicacile okutholakele kulolu cwaningo ukuthi amazinga okuqala e-DNA yesimila esijikelezayo (ctDNA) ngaphambi kokuqala ukwelashwa nge-immunotherapy anenani elikhulu lokubikezela. Iziguli ezinamazinga aphansi e-DNA yesimila esijikelezayo ekuqaleni kokwelashwa zibonise ukusinda okukhulu okungenalo inqubekela phambili kanye nokusinda isikhathi eside uma kuqhathaniswa nalezo ezinamazinga aphezulu.
Kusukela ngaleso sikhathi kuqhubeke, ukuqapha ukuvela kwe-ctDNA emasontweni ambalwa okuqala kwabonakala kwembula okufanayo. Cishe amasonto amathathu ngemva kokuqala ukwelashwa nge-immunotherapy, izinguquko emazingeni e-ctDNA kakade zihlobene nokulawulwa kwezifo: ukwehla okukhulu kwahlotshaniswa nokusabela okungcono, kuyilapho amazinga azinzile noma akhulayo asikisela ukuthi isimiso somzimba sokuzivikela sasingakwazi ukuvimba isimila.
Okuthakazelisa kakhulu ukubona ukuthi ukunyamalala okuphelele kwe-DNA yesimila egazini , nganoma yisiphi isikhathi ngesikhathi sokulandelela, kwakuhlotshaniswa njalo nokusabela ngemisebe kanye nokusinda isikhathi eside. Ngamanye amazwi, lapho i-ctDNA ingasatholakali, amathuba okuthi i-immunotherapy isebenze kahle ayephezulu kakhulu.
Empeleni, lolu lwazi luvumela ukuhlolwa kwasekuqaleni kokuthi ukwelashwa kuyasebenza yini, ngaphandle kokulinda izinguquko ukuthi zibonakale ekuhlolweni kwezithombe okuvamile. Ezigulini ezisesigabeni esiphezulu, leli khono lokubona kusengaphambili impendulo noma ukuntuleka kwayo kungenza umehluko omkhulu uma kuziwa ekugcineni noma ekushintsheni isu lokwelapha.
Abacwaningi bagcizelela ukuthi konke lokhu kwenzeke ngokusebenzisa amasu okulandelana abucayi kakhulu , akwazi ukubona izingxenyana ezincane ze-DNA yesimila ku-plasma. Le ndlela ebucayi kakhulu ibalulekile ekubambeni ukwehluka okuncane kodwa okubalulekile emtholampilo emthwalweni wesimila ojikelezayo.
Ukuhlukanisa phakathi kokuqhubeka kwangempela kanye nokuqhubeka mbumbulu: inselele ebalulekile yezokwelapha
Ngaphandle kokubikezela ukusinda kanye nokusabela, ukuguquguquka kwe-DNA yesimila esijikelezayo kunikeza usizo olubalulekile ekuxazululeni enye yezinselele ezivamile ekwelashweni nge-immunotherapy: ukuhlukanisa phakathi kokuqhubeka kwesimila sangempela kanye nokuqhubeka kwe-pseudoprogression . Lesi sakamuva yisimo lapho izithombe zibonakala zibonisa ukwanda kosayizi wesilonda, kodwa empeleni lokhu kungenxa yokungena kwamaseli omzimba ahlasela isimila.
Ngezindlela ezijwayelekile zokuthwebula izithombe, njenge- computed tomography , ukuhumusha lezi zimo akulula ngaso sonke isikhathi. Kwezinye izimo, ukubukeka kwe-radiological kungasikisela ukuthi lesi sifo siya siba sibi kakhulu lapho, empeleni, ukwelashwa kuqala ukusebenza. I-Ultrasensitive liquid biopsy inikeza ungqimba olwengeziwe lolwazi: uma izinga le-cytotoxic DNA (ctDNA) lehla, kungenzeka kakhulu ukuthi sibona i-pseudoprogression kunokwehluleka kokwelashwa.
Ngokusho kwabalobi bocwaningo, leli khono le-liquid biopsy lokuhlaziya ukuchazwa kwesithombe liwusizo ikakhulukazi ezimweni lapho izilonda ziziphatha ngokungacacile ekuhlolweni kwe-radiological. Lapho amazinga e-cytotoxic DNA (ctDNA) ekhuphuka kancane kancane, amathuba okuqhubeka kwesimila aphakeme kakhulu, okusekela isidingo sokuhlola kabusha ukwelashwa.
Ngaphezu kwalokho, ukuhlaziywa okulandelanayo kwe-ctDNA kusize ekubikezeleni ukuvela kweziguli eziqhubeka nokwelashwa nge-immunotherapy ngale kokuqhubeka kokuqala okubonakalayo . Kulezi zimo, ukuqapha amazinga e-ctDNA eduze kwenze kwaba nokwenzeka ukuhlonza ukuthi obani abangaqhubeka nokuzuza ekwelashweni nokuthi ubani okungenzeka angakuzuzi.
Ngokombono ongokoqobo, konke lokhu kuhunyushwa kube ithuluzi elithuthukisa ukwahlukaniswa kweziguli kusenesikhathi kanye nokuqapha okuqhubekayo kokusabela, okunikeza amaqembu emitholampilo izinto eziningi zokunquma ukuthi aqhubeke nokwelashwa okuqhubekayo, akuhlanganise nezinye izinketho, noma ashintshe ngokuphelele isu.
Izinzuzo ngaphezu kwamasu ezithombe avamile
Ucwaningo luphinde lwaqhathanisa ukuqapha kusetshenziswa i-ultrasensitive liquid biopsy nokuhlola okujwayelekile okusekelwe ekuhlolweni kwezithombe, ikakhulukazi ama-CT scan. Nakuba amasu e-radiological esabalulekile, abacwaningi bathole ukuthi ukuhlaziywa kwe-CTDNA kungathola izinguquko kulesi sifo ezingabonakali kahle ngaso sonke isikhathi ekuthathweni kwezithombe.
Enye yezinzuzo ezivame ukukhulunywa yithimba ukuthi i-liquid biopsy, njengoba ingangenisi umdlavuza, ingaphindaphindwa kaningi ngangokunokwenzeka ngaphandle kokubeka isiguli emisebeni eyengeziwe noma ezinqubweni eziyinkimbinkimbi. Ngokuphambene nalokho, ngokuvamile kuyadingeka ukulinda phakathi kokuskena okukodwa kwe-CT nokulandelayo, kokubili ngenxa yezizathu zokuphepha nezokuthutha.
Lokhu kwazi ukuthatha amasampula njalo kuvula ithuba lokuqapha isimila ngendlela enamandla kakhulu. Uma amazinga e-ctDNA eqala ukukhuphuka, isaziso siqaliswa kusenesikhathi, ngisho nangaphambi kokuba kubonakale ukuqhubekela phambili ekuthathweni kwezithombe. Ngokuphambene nalokho, uma ehla noma ehlala ephansi kakhulu, kwandisa ukuzethemba kokuthi ukwelashwa nge-immunotherapy kuyasebenza, okungavimbela izinguquko zokwelapha ngaphambi kwesikhathi.
Abacwaningi bagcizelela ukuthi, kwezinye izimo, i-liquid biopsy yabavumela ukuthi babone izimpendulo kanye nokuqhubeka okwakufihliwe ngaphambilini endaweni engwevu ekuthathweni kwezithombe. Lokhu kubaluleke kakhulu ezilondeni ezincane, okunzima ukuzilinganisa ngokunemba kwe-radiological, noma ezigulini ezine-metastases eziningi ezithweni ezahlukene, lapho ukuchazwa okuphelele kungaba nzima kakhulu.
Nakuba umgomo ungekona ukufaka esikhundleni ngokuphelele izivivinyo zezithombe, iqembu le-VHIO liphakamisa ukuthi inhlanganisela ehlakaniphile yazo zombili izindlela inganikeza ukuqapha kwesiguli okuphelele futhi okungadingi ukungenelela okuningi, kwezinye izimo kunciphisa isidingo sokuhlolwa okuningi okuphindaphindiwe ngemisebe.
Iphrojekthi yaseYurophu egxile ekuhumusheni
Imiphumela eshicilelwe imele idatha yokuqala ehlanganisiwe evela ku-IMMUNOMICS-VHIO , ipulatifomu yocwaningo egxile ekutholakaleni nasekuqinisekisweni kwama-biomarker e-immunotherapy, okuyingxenye yohlelo lwe-CAIMI lwe-VHIO. Umgomo wokugcina walo msebenzi ukuthi la mathuluzi adlulele ngale kwendawo yokuhlola ngokuqinile futhi, ngokuhamba kwesikhathi, ahlanganiswe nomkhuba ojwayelekile wezokwelapha.
Ilabhorethri kaRodrigo Toledo, ehola ukuthuthukiswa kwalezi zindlela zokuhlola uketshezi ezibucayi kakhulu , isekelwa yi-FERO Foundation futhi isebenzisana nezinhlelo ezifana ne-PREDICT, ezigxile ekwenzeni impendulo yokwelashwa nge-immunotherapy ibe ngeyakho kusetshenziswa izithombe kanye nama-biomarker ama-molecule. Lokhu kuphinde kuhambisane nokubamba iqhaza ezinhlanganweni zaseYurophu ezifana ne-DART kanye ne-UpSMART Accelerator, ezihlose ukusheshisa ukuhunyushwa kwalezi ntuthuko emisebenzini yansuku zonke yeziguli ezinomdlavuza.
I-VHIO igcizelela ukuthi, yize imiphumela ithembisa kakhulu, lokhu okubonwe kusadingeka kuqinisekiswe kuma-cohorts amasha nasezindaweni ezibanzi zezokwelapha. Kuze kube manje, ubufakazi obuningi bukhiqizwe ezivivinyweni zesigaba 1, ngenani elikhulu lamasampula kodwa endaweni yocwaningo elawulwa kakhulu.
Enye inselele esele ukwenza lezi zinkundla zibe ezingabizi kakhulu futhi zikwazi ukwandiswa ukuze zisetshenziswe ezibhedlela ezinobunzima obuhlukahlukene, hhayi nje ezikhungweni zokudlulisela ezikhethekile kakhulu. Umgomo uwukuba ulwazi olufanayo oluningiliziwe olutholakala njengamanje esivivinyweni somtholampilo lutholakale, esikhathini esimaphakathi, ezigulini ezithola ukwelashwa nge-immunotherapy emikhubeni ejwayelekile yezokwelapha.
Ngesikhathi esifanayo, ithimba liyaqhubeka nokuthuthukisa ukulandelana kanye namasu okuhlaziya i-bioinformatics ukuze lithole okuningi kusampula ngayinye yegazi, lihlonza amaphethini e-ctDNA angabonisi nje kuphela ukuthi ukwelashwa kuyasebenza noma cha, kodwa futhi asize ekuqondeni kangcono izindlela zokumelana nomdlavuza kanye nokuklama inhlanganisela yokwelapha ephumelela kakhulu.
Yonke le mizamo ibeka i-biopsy yoketshezi ezwela kakhulu njengengxenye ebalulekile ekuguqukeni kwe -oncology eyenzelwe umuntu ngamunye , lapho izinqumo zingasekelwe kuphela ohlotsheni lwesimila nendawo yaso, kodwa futhi nasekushintsheni kwesimo saso sama-molecule ngokuhamba kwesikhathi kanye nokwelashwa ngakunye.
Ngemininingwane etholakalayo, i-biopsy yoketshezi ebucayi kakhulu iyavela njengethuluzi elinamandla amakhulu okuhlonza ukuthi yiziphi iziguli zomdlavuza ezingazuza ekwelashweni nge-immunotherapy , ukuqapha ngokuseduze ukuvela kwesimila, nokusiza ukuhlukanisa izimo eziyinkimbinkimbi njenge-pseudoprogression ekuqhubekeni kwangempela. Nakuba kusenezinyathelo ezibalulekile ngaphambi kokuba ifakwe njalo emisebenzini yezokwelapha, umsebenzi ohlanganisiwe ovela ku-VHIO kanye nabalingani bayo baseYurophu ukhomba esimweni lapho ukukhishwa kwegazi okulula kunganikeza ulwazi olubalulekile lokulungisa, ukugcina, noma ukushintsha ukwelashwa, ngenhloso yokunikeza isiguli ngasinye inketho yokwelapha efaneleka kakhulu kwi-biology yesifo sabo.
