I-biopsies yamanzi isebenzisa igazi-kungekhona izicubu zesisu-ukufumanisa umdlavuza
Ngokuqhelekileyo, iimvumi zihlolwa ngokusebenzisa i-biopsies yamathambo. Isampuli encinci ithathwa kwi-tumor kunye ne-genotyped, okanye ihlaziywe ukuveliswa kwemfuza. Ingxaki ngale ndlela kukuba izicubu ezinobungozi zinokuba nzima. Ukongezelela, i-biopsy tumor inikezela kuphela umfanekiso wesisu.
Ukubhala kwi- Medicine Discovery ngo-2015, uLabgaa kunye nabalobi-mbambano bathetha oku okulandelayo malunga ne-biopsy yesiqhelo:
Ngezizathu ezicacileyo, kunzima ukujonga ukuguquka kwesisu kunye ne-biopsies efanayo. Kwakhona, i-biopsy kuphela izibuko zendawo enye ye-tumor kwaye ngoko akunakwenzeka ukuba ibonise yonke into eguquguquka yimizimba emathunjini amakhulu. Enye indlela eya kuba kukufumana i-biopsies ezininzi kwi-tumor efanayo, kodwa olu khetho alubonakali lichanekile kwaye alunene.
I-biopsy yamanzi ibandakanya ukulinganisa i-DNA (ctDNA) kunye nezinye izidumbu zeplastiki ezifunyenwe kwizigulane ezinomdlavuza. Indlela evelayo yokuxilonga ithembisa ukukhawuleza, ukungabonakali, kunye neendleko.
Imbali yoBuquid Biopsy
Ngowe-1948, i-Mandel neMétais, abaphandi abaFrentshi baqale bafumanisa i-ADNA kwigazi labantu abaphilileyo. Oku kufumaniswe ngaphambili kwexesha layo, kwaye kwakungekho emva kweeminyaka emashumi ukuba i-ADNA iqhutywe kwakhona.
Ngowe-1977, uLeon kunye nabalingane bakhe baqala ukufumana inani elongezelelweyo le-CDN kwigazi lezigulane zomhlaza.
Ngama-1989, iStroun kunye nabalingane abachongiweyo be-neoplastic (oko kukuthi, umhlaza) kwigazi. Emva kokufunyaniswa, amanye amaqela athile achaza utshintsho oluthile kwi-tumor suppressors kunye ne-oncogenes, ukungazinzi kwe-microsatellite kunye ne-DNA methylation, ebonise ukuba i-ctNA ikhutshwe kwi-tumor.
Nangona siyazi ukuba i-ctDNA ephuma kwiiseli zesisu ijikeleza egazini, imvelaphi, izinga lokukhululwa, kunye nendlela yokukhululwa kwale DNA ayibonakali, kwaye uphando lubangela iziphumo eziphikisanayo. Olunye uphando lubonisa ukuba ezinye izicubu ezinobungozi ziqulethe ii-cell cells ezifa kwaye zikhulule i-ctDNA. Nangona kunjalo, uphando oluthile lubonisa ukuba zonke iiseli zikhulula i-ctDNA. Nangona kunjalo, kubonakala ngathi izicubu zomhlaza zikhulula amanqanaba e-CD kwigazi, okwenza i-ctDNA ibe yinto efanelekileyo yomhlaza.
Ngenxa yokwahlula kakhulu kunye namaqondo aphantsi egazini, i-ctDI kunzima ukuhlukanisa kunye nokuhlalutya. Kukho ukungafani kwamanani e-ADN phakathi kweesumum kunye neesampula ze-plasma. Kubonakala sengathi i-serum yegazi esikhundleni se-plasma yegazi ngumthombo ongcono we-CDN. Kwisifundo se-Umetani kunye nabalingane, i-ADT concentrations yafunyaniswa ukuba ihlale iphantsi kwi-plasma xa kuthelekiswa ne-serum ngenxa yokulahleka kwe-DNA ngexesha lokuhlanjululwa, njengoko i-coagulation kunye nezinye iiprotheni ziyacinywa ngexesha lokulungiselela.
Ngokutsho kwe-Heitzer kunye noogxa nabo, nayi imicimbi ethile ekufuneka ixazululwe ukuba idibanise i-ctNA:
Okokuqala, iinkqubo zangaphambili zifuna ukuba zilungelelwe .... Ukukhethwa kwendlela yokuzihlukanisa eqinisekisa ukukhutshwa kwexabiso elaneleyo le-DNA eliphezulu kwaye liboniswe ukuba izinto zokuqala zeempendulo zegazi kunye nokuqhutyelwa kwegazi zingathintela kakhulu i-DNA isivuno .... Okwesibini, enye yeyona nto ibaluleke kakhulu kukungabikho kokuvumelanisa kweendlela zokubala. Iinkqubo ezahlukeneyo zokubala, ... zivelise iziphumo ezahlukeneyo kuba le milinganiselo ijolise kwiDNA okanye i-DNA kuphela. Okwesithathu, kuncinci kwaziwa malunga nemvelaphi kunye nendlela ecacileyo yokukhutshwa kwe-CDN, kwaye kwiinkalo ezininzi ezidibanisa iziganeko ezinokubangela ukukhutshwa kwe-CDN.
Iindlela ezijoliswe kuMgaqo-nkqubo
Okwangoku, kukho iindlela ezimbini ezibalulekileyo ezithathwe xa kuhlaziywa i-plasma yegazi (okanye i-serum) ye-CDN. Indlela yokuqala ijoliswe kwaye ikhangelele utshintsho oluthile lwezityalo ezibonakalisa izicubu. Indlela yesibini ayilindelekanga kwaye iquka ukuhlalutya kwe-genome ukujonga i-ctDNA ebonakalisa umdlavuza. Ngenye indlela, ukulandelelaniswa kwindlela esetyenzisiweyo njengendlela yokusebenzisa imali eninzi, engayilindelekanga. Iimpahla ziyingxenye zeDNA ezibhaliselwe ukwenza iprotheni.
Ngeendlela ezijoliswe kuzo, i-serum ihlaziywa ngenxa yenguqu eyaziwayo yemfuza kwisethi encinci yokutshintshwa komqhubi.
Ukuguquka komqhubi kubhekisela kwimitshintsho kwi-genome ekhuthaza, okanye "ukuqhuba," ukukhula kwamaseli omhlaza. Ezi zinguqu ziquka iKRAS okanye i- EGFR .
Ngenxa yentuthuko yezobuchwepheshe kwiminyaka yamuva, iindlela ezijoliswe kuhlalutyo lwe-genome kwiimali ezincinci ze-ctDNA ziye zenzeke. Olu buchwepheshe buquka i-ARMS (ukuphucula ukuguqulwa kwenkqubo yokuguquka); I-PCR yedijithali (dPCR); ububanzi, imulsion, ukukhulisa, kunye ne-magnetics (BEAMing); kunye nokulandelelana okunzulu (CAPP-Seq).
Nangona kukho inkqubela phambili kwezobuchwephesha eyenza indlela ejoliswe kuyo, indlela ejoliswe kuyo ijolise kuphela kwizikhundla ezimbalwa zokutshintshwa kwezinto (iindawo ezihamba phambili) kwaye ilahlekelwa ezininzi zinguqu zogqirha ezifana ne-tumor suppressor genes.
Inzuzo eyintloko yeendlela ezingalindelekanga kwi-biopsy yamanzi kukuba zingasetyenziselwa kuzo zonke izigulane ngenxa yokuba uvavanyo aluxhomekeke kwimitshintsho ye-genetic ephindaphindiweyo. Utshintsho lwezakhi zofuzo oluqhelekileyo alugubungele zonke i-cancer kwaye azibonakalisi zisesayinini zomhlaza. Nangona kunjalo, le ndlela ayinako ukuhlalutya ukuqonda kunye nokuhlalutya ngokubanzi kwe-genomes ye-tumor ayikwanakwenzeka.
Ingqalelo, ixabiso lokulandelelanisa i-genome lonke liye lahla. Ngo-2006, intengo yokulandelelanisa i-genome yonke yayingama-dollar ayi-300,000 (i-USD). Ngo-2017, iindleko zaye zawela kuma-dollar ayi-1 000 (i-USD) nge-genome nganye, kubandakanywa izigulane kunye nokuqulunqwa koomatshini bokulandelela.
Uncedo lwezonyango lwe-Biopsy
Imizamo yokuqala yokusebenzisa i-ctDNA yayiyi-diagnostic kwaye ifaniswe amanqanaba kwizigulane eziphilileyo kunye nezogulane zomhlaza okanye abo abanezifo eziqatha. Iziphumo zale migudu zaxutywa, kunye nezifundo ezithile ezibonisa ukungafani okwakubonisa umdlavuza, isimo esingenazifo, okanye ukubuyela kwakhona.
Isizathu sokuba i-ctNA ingasetyenziselwa kuphela ixesha lokuxilonga umdlavuza kuba ixabiso elinganayo le-ctDNA livela kwiisisu. Azikho zonke izicubu "eziphalaza" i-DNA inomlinganiselo ofanayo. Ngokubanzi, eziphambili, iifama ezixhaphakileyo zichithe i-DNA ngakumbi kwi-circulation ngaphezu kwexesha elide, elikulo ndawo, izidumbu. Ukongezelela, iintlobo ezahlukeneyo zeengcambu zichitha iindidi ezahlukeneyo zeDNA kwi-circulation. Ingqungquthela yokujikeleza i-DNA ephuma kwi-tumor iyahlukahluka ngokubanzi kwizifundo kunye neentlobo zomhlaza, ukusuka kwi-0.01% ukuya kwi-93%. Kubalulekile ukuba uqaphele ukuba, ngokubanzi, kuphela umncinci we-ctDNA ovela kwi-tumor, yonke into evela kwizicubu eziqhelekileyo.
Ukujikeleza i-DNA ingasetyenziselwa umqondiso wesifo. Ukujikeleza i-DNA ingasetyenziswa ukujonga utshintsho lomhlaza emva kwexesha. Ngokomzekelo, uphando oluthile lubonise ukuba izinga lokusinda kweminyaka emibini kwizigulane ezinomhlaza ongqambileyo (oko kukuthi, inani lezigulane zisaphila ubuncinane kwiminyaka emibini emva kokuxilongwa ngumhlaza omninzi) kunye nokuguquka kwe- KRAS hotspot kwaba yi-100 ekhulwini kulabo bengenabo ubungqina DNA ejikelezayo. Ngaphezu koko, kwenzeka ukuba kwikamva elikufutshane, ukujikeleza kweDNA kunokusetyenziswa ukujonga iilonda ezinqabileyo.
Ukujikeleza i-DNA ingasetyenziselwa ukujonga ukuphendula kwonyango. Ngenxa yokuhambisa i-DNA imifanekiso ebhetele ngokubanzi yokuvelisa izidumbu, le DNA cishe iqukethe i-DNA yokuxilonga, engasetyenziselwa endaweni yesifo seDNA esivela kwiimathumba ngokwazo.
Ngoku, makhe sijonge kwiimpawu ezithile ze-biopsy yamanzi.
Guardant360
Ezempilo zoLondolozo zenze uvavanyo olusebenzisa ukulandelelaniswa kwesizukulwana esilandelayo kwiprofayili ejikeleza i-DNA yokutshintshwa kwemvelo kunye ne-chromosomal rearrangements kuma-gene ahlobene neengcambu ezingama-73. I-Guardant Health yashicilela isifundo esichaza ukusetyenziswa kwe-biopsy yamanzi kwi-oncology. Isifundo sasebenzisa iisampuli zegazi ukusuka kwizigulane ezingama-15,000 ezineentlobo ezi-50 zee-tumor.
Ngokona buninzi, iziphumo ezivela kuvavanyo lwe-biopsy lwamanzi oluhambelana nokuguqulwa kwemizimba ephawulwe kwi-biops.
Ngokutsho kweNIH:
U-Guardant360 ufumene utshintsho olufanayo olubalulekileyo kwiijethi ezinxulumene nomhlaza ezifana ne- EGFR, i-BRAF, i- KRAS kunye ne- PIK3CA kwiimpawu ezifana neento ezazifunyenwe ngaphambili kwiisampuli ze-biopsy, i-statistically ihambelana nama-94% ukuya kuma-99%.
Ngaphezu koko, ngokwe-NIH abaphandi babika oku okulandelayo:
Kwisigaba sesibini sophando, abaphandi bavavanya izigulane ezingaba ngu-400-uninzi lwazo lwaluphethe ummiphu okanye umdlavuza omnxeba-oye wafumana i-CD ctDNA kunye ne-tumor tissue tissue DNA zifumaneka kwaye zithelekisa iipatheni zokutshintsha kwe-genomic. Ukuchaneka ngokubanzi kwe-biopsy yamanzi xa kuthelekiswa neziphumo ezivela kuhlalutyo lwe-biopsy i-87%. Ukuchaneka kwanda kuma-98% xa igazi kunye neesampuli ze-tumor ziqokelelwa kwiinyanga ezili-6 zomnye.
I-Guardant360 ichanekile nangona amazinga okujikeleza i-DNA egazini aphantsi. Izihlandlo eziqhelekileyo, ukujikeleza i-DNA ye-tumor kuyenziwe i-0.4 ekhulwini ye-DNA egazini.
Ngokubanzi, kusetyenziswa i-biopsy yamanzi, abaphandi abaLondolozi banakho ukufumanisa amanqaku amathumba angakhokelela unyango ngamagqirha kuma-67 eepesenti zezigulane. Ezi zi gulane zifanelekile zonyango oluvunyiweyo lwe-FDA kwakunye neendlela zokuphanda.
iCNA kunye neLung Cancer
Ngo-2016, i-FDA ivume i-cobas EGFR Mutation Test to use for the detection of EGFR mutations kwiDNA ejikelezayo yezigulane zomhlaza wemiphunga. Olu vavanyo lwaluyi-biopsy yokuqala evunyiweyo ye-FDA kwaye ichonge izigulane ezinokuthi zibe ngabaviwa kwiinkqubo ezijoliswe ku-erlotinib (Tarceva), afatinib (Gilotrif), kunye ne-gefitinib (Iressa) njengonyango lokuqala, kunye ne-osimeritinib (iTrrisso) unyango lwe sibini. Ezi zijoliswe kumathambo ehlaselo lomhlaza weeseli kunye noguquko oluthile lwe- EGFR .
Kubaluleke kakhulu, ngenxa yenani eliphakamileyo leempembelelo ezingamanga, i-FDA icebisa ukuba isampuli ye-biopsy isathathwa kwisigulane esinesifo esibi se-biopsy.
i-CDN ne-Cancer Cancer
Inani labantu ababulawa ngumhlaza wesibindi sele landisiwe kwiminyaka engama-20 edlulileyo. Okwangoku, umdlavuza wesibindi yimbangela yesibini ebangela ukuba umdlavuza afe emhlabeni. Akukho zixhobo ezibonakalayo ezifumanekayo ukufumana nokuhlaziya isibindi, okanye i-hepatocellular (HCC), umhlaza. Ukujikeleza i-DNA ingaba yinto efanelekileyo ye-biomarker yomhlaza wesibindi.
Cinga le ngcaciso elandelayo esuka eLagbaa kunye nababhali-mbhali malunga nokusetyenziswa kokusebenzisa i-DNA ukuxilonga umdlavuza wesibindi:
I-Hypermethylation ye-RASSF1A, i-p15, kunye ne-p16 iye yaphakanyiswa njengezixhobo zokuxilonga kwangaphambili kwisifundo esiphendulelayo kubandakanya izigulane ezingama-50 ze-HCC. Iisayine ezine ezine-gene (i-APC, i-GSTP1, i-RASSF1A, i-SFRP1) kwaye ihlolwe ukuchaneka ngokuchanekileyo, ngelixa i-methylation ye-RASSF1A ibikwa njenge-biomarker yeprognostic. Ucwaningo oluthile luhlalutya i-ADN kwii-HCC izigulane zisebenzisa ubuchwephesha obunzulu bokulandelela .... Ngokugqithiseleyo, iinombolo ze-DNA ezikhohlakeleyo zifunyenwe kwizithuthi ezimbini ze-HBV ngaphandle kwembali yangaphambili ye-HCC ngexesha lokuqokelela igazi, kodwa ngubani owaphuhlisa i-HCC ngexesha lokulandelelana. Oku kufunyenwe kwavula umnyango wokuvavanya ikopi yenombolo kwi-ctNNA njengesixhobo sokuhlola ukuqala kweHCC.
ILizwi
I-biopsies yamanzi iyindlela entsha enomdla wokuxilongwa kwe-genomic. Okwangoku, ezinye ii-biopsies ezithile zamanzi, ezinikezela ngokucacisa i-molecular profilo, zifumaneka kumayeza ukuba azalise ulwazi lofuzo olufunyenwe kwi-biopsy yamathambo. Kukho ezinye i-biopsies ezithile zamanzi ezingasetyenziselwa indawo ye-biopsy ye-tissu-xa i-biopsies zenyama zingekho.
Kubalulekile ukugcina engqondweni ukuba ezininzi izilingo ze-biopsy ziqhubekayo kwaye uphando olongezelelweyo lufuneka lwenziwa kwinyama ngaphandle kwendlela yokwenza uphuhliso lwangenelelo.
> Imithombo:
> Ukuhlolwa kwegazi ngenxa yeenguqu ze-Genetic in Tumors Kubonisa isithembiso njengenye indlela yokuxhamla i-Biopsy. NIH.
> Heitzer E, Ulz P, Geigl JB. Ukujikeleza i-DNA ye-Tumor njenge-Liquid Biopsy yeCarcer. Chemistry Clinic. 2015; 61: 112-123. i-doi: 10.1373 / iklinikhi yekliniki.2014.222679
> I-Lagbaa J, iVillanueva A. I-biopsy inkunkuma kwisifo somhlaza. Ukufumana unyango. 2015; 19 (105): 263-73.
> I-Liquid Biopsy: Ukusebenzisa i-DNA kwiGazi yokuThola, ukuPhepha, nokuPhatha umdlavuza. NIH.
> Umetani N, et al. Inani eliphakamileyo le-DNA ejikelezayo kwi-serum ngaphezu kwiplasma akubangelwa yi-DNA engcolileyo ngexesha lokuhlukana. Ann NY Acad Sci. 2006; 1075: 299-307.
> Wellstein A. Imigaqo-siseko kwi-Pharmacotherapy yeCarcer. Ku: Brunton LL, Hilal-Dandan R, Knollmann BC. eds. Goodman & Gilman's: I-Pharmacological Basis yeTherapeutics, 13e eNew York, NY: iMcGraw-Hill.