Ma biopsies amadzimadzi amagwiritsira ntchito magazi osati ziwalo zamatenda-kuti apeze khansa
Kawirikawiri, matendawa amafufuzidwa pogwiritsa ntchito zizindikiro za minofu. Chitsanzo chaching'ono chimatengedwa kuchokera ku chotupa ndi genotyped, kapena kufufuza kwa maonekedwe a majini. Vuto ndi njirayi ndikuti zotupa zowopsya zingakhale zovuta. Kuwonjezera apo, chotupa chophweteka chimapereka chithunzi chokhacho cha chotupacho.
Kulemba mu Discovery Medicine mu 2015, Labgaa ndi olemba anzawo amanena izi zokhudzana ndi chotupa chodziwika bwino:
Pa zifukwa zomveka, n'zovuta kuyang'ana zamoyo zokhudzana ndi vutoli. Komanso, biopsy imangoonetsa malo amodzi okhawo ndipo sizingatheke kuimira kusintha kwakukulu kambiri m'matumbo akuluakulu. Njira ina idzakhala yopeza ma biopsies ambiri pa chotupa chomwecho, koma njirayi ikuwoneka kuti si yeniyeni kapena yolondola.
Madzi amadzimadzi amatanthauza kuchulukitsa DNA (ctDNA) ndi mankhwala ena otupa m'magazi omwe amapezeka kwa odwala khansa. Njira yowonetsera njirayi ikulonjeza kuti idzafulumira, yopanda mphamvu, komanso yotsika mtengo.
Mbiri ya Zamadzimadzi Zamadzimadzi
Mu 1948, Mandel ndi Métais, awiri ofufuza a ku France adayamba kuzindikira ctDNA m'mwazi wa anthu wathanzi. Kupeza kumeneku kunali patsogolo pa nthawi yake, ndipo pasanathe zaka makumi angapo, ctDNA inafufuzidwa.
Mu 1977, Leon ndi anzake adayamba kuzindikira kuchuluka kwa ctDNA m'magazi a odwala khansa.
Pofika m'chaka cha 1989, Mgwirizano ndi anzako amagwirizana ndi ziwalo za khansa (ie, khansa) m'magazi. Zitatha izi, magulu angapo ambiri adasintha kusintha kwa chifuwa chachikulu chotchedwa tumor suppressors ndi oncogenes, kuchepa kwa microsatellite, ndi DNA methylation, zomwe zinatsimikizira kuti ctDNA imamasulidwa kuti iyambe kufalitsa.
Ngakhale tikudziŵa kuti ctDNA yotengedwa ndi maselo amagazi imayambira m'magazi, chiyambi, mlingo womasuka, ndi njira yotulutsira DNA iyi sizikudziwika, ndi kufufuza kumabweretsa zotsatira zotsutsana. Kafukufuku wina amasonyeza kuti zotupa zowopsa kwambiri zili ndi maselo ambiri a khansa zakufa ndipo zimamasula ctDNA. Komabe, kafukufuku wina amasonyeza kuti maselo onse amasulidwa ctDNA. Komabe, zikuwoneka kuti zotupa za khansa zimatulutsa kuchuluka kwa ctDNA m'magazi, kupanga ctDNA kukhala chidziwitso chabwino cha khansa.
Chifukwa cha kugawidwa kwakukulu ndi kuchepa kwa magazi, ctDNA ndi yovuta kudzipatula ndikuyesa. Pali kusiyana kwa ctDNA pakati pa seramu ndi plasma zitsanzo. Zikuwoneka kuti seramu ya magazi m'malo mwa plasma ya magazi ndi gwero labwino la ctDNA. Mu phunziro la Umetani ndi anzake, magulu a ctDNA amapezeka kuti ali otsika kwambiri mu plasma poyerekeza ndi seramu chifukwa chotheka kutaya DNA poyeretsa, pamene mapuloteni ndi mapuloteni ena akuchotsedwa panthawi yokonzekera.
Malingana ndi Heitzer ndi anzake, apa pali nkhani zina zomwe ziyenera kuthandizidwa kuti zikhale ndi zotsatira za matenda a ctDNA:
Choyamba, njira zowonongeka zimayenera kukhala zofanana .... Kusankha njira yodzipatula yomwe imathandiza kuti DNA ikhale yamtengo wapatali kwambiri ndipo ikuwonetseratu kuti zowonongeka za zitsanzo zamagazi ndi kusinthika zingakhudze kwambiri DNA .... Chachiwiri, chimodzi mwa zinthu zofunika kwambiri ndi kusowa kwa kugwirizana kwa njira zogwiritsira ntchito. Njira zosiyana zogwiritsira ntchito, ... zimabweretsa zotsatira zosiyana chifukwa izi zimagwiritsidwa ntchito ndi DNA yeniyeni kapena yokhayokha. Chachitatu, zochepa zimadziwika za chiyambi ndi ndondomeko ya ctDNA kumasulidwa, ndipo mu maphunziro ambiri amachititsa chidwi zochitika zomwe zingathandizenso kutulutsa ctDNA.
Njira zoyendetsedwa ndi Zomwe Sizinachitike
Pakalipano, pali njira zikuluzikulu ziwiri zomwe zimachitika pofufuza magazi a plasma (kapena seramu) a ctDNA. Njira yoyamba ikuwongolera ndikuyang'ana kusintha komwe kumayambitsa maumimba. Njira yachiwiri imakhala yosayimilira ndipo imaphatikizapo kusanthula kwa thupi lonse kuyang'ana ctDNA yowonetsa khansa. Mwinanso, kuyesa kusankhidwa kwagwiritsidwa ntchito ngati njira yopanda malire, yopanda malire. Zochokera kumalo ndi mbali za DNA zomwe zimasindikizidwa kuti apange mapuloteni.
Ndi njira zowonongeka, seramu imafufuzidwa chifukwa cha zidziwitso za genetic mutations mu kagulu kakang'ono kamasintha kagetsi.
Kusintha kwa galimoto kumatanthawuza kusintha kwa ma genome komwe kumalimbikitsa, kapena "kuyendetsa galimoto," kukula kwa maselo a khansa. Zosintha izi zikuphatikizapo KRAS kapena EGFR .
Chifukwa cha kupita patsogolo kwa sayansi m'zaka zaposachedwa, njira zowonetsera za mtundu wa genome za ctDNA zingakhale zotheka. Zipangizo zamakonozi zikuphatikizapo ARMS (amplification refractory mutation system); digito PCR (dPCR); mikanda, emulsions, amplification, ndi magnetics (BEAMing); komanso kusamvana kwakukulu (CAPP-Seq).
Ngakhale kuti zipangizo zamakono zakhala zikupita patsogolo, zomwe zimawoneka kuti zitha kuchitika, zimangowonjezera malo ochepa omwe amachititsa kusintha mthupi mwawo ndipo zimasowa kusintha kwa maulendo osiyanasiyana monga chifuwa choyambitsa matenda.
Phindu lalikulu la njira zosawerengedwera zowonjezera madzi ndizomwe zingagwiritsidwe ntchito kwa odwala onse chifukwa chakuti mayesero sangadalire kusintha kwasinthika kwa majini. Kusinthika kwa majini kawirikawiri sikukuphimba khansa zonse ndipo sizomwe zimayambitsa khansa yeniyeni. Komabe, njirayi silingathe kulingalira mozama komanso kuganizira mozama za mankhwala otupa m'mimba sizingatheke.
Zindikirani, mtengo wogwiritsira ntchito mtundu wonse wa genome wagwera kwambiri. Mu 2006, mtengo wogwiritsira ntchito majeremusi onse unali pafupifupi madola 300,000 (USD). Pofika chaka cha 2017, ndalamazo zinagwera pafupifupi madola 1,000 (USD) pa genome, kuphatikizapo reagents ndi kubwezeretsa makina oyang'anira.
Kusamalira Mankhwala Osokoneza Bongo
Ntchito yoyamba yogwiritsira ntchito ctDNA inali yodziŵika ndi kuyerekezera odwala omwe ali ndi matenda a khansa kapena omwe ali ndi matenda oopsa. Zotsatira za zoyesayesazi zinali zosakanikirana, ndi maphunziro ena okha omwe amasonyeza kusiyana kwakukulu komwe kumasonyeza khansara, kukhalabe ndi matenda, kapena kubwereranso.
Chifukwa chomwe ctDNA ingagwiritsire ntchito kokha nthawi yodziwira khansara ndi chifukwa kuchuluka kwa ctDNA kumachokera ku zotupa. Sikuti matenda onse "anakhetsa" DNA mofanana. Kawirikawiri, zotupa kwambiri, zotuluka m'magazi zinapangitsa kuti DNA ikhale yofala kwambiri kusiyana ndi yoyamba, malo amodzi, matumbo. Kuwonjezera apo, mitundu yosiyanasiyana ya zotupa imayambitsa mitundu yosiyanasiyana ya DNA m'kufalitsidwa. Chigawo chochepa chozungulira DNA chomwe chimachokera ku chotupacho chimakhala chosiyana kwambiri pakati pa maphunziro ndi mitundu ya khansa, kuyambira 0.01% mpaka 93%. Ndikofunika kuzindikira kuti, kawirikawiri, kokha kokha ka ctDNA kamachokera ku chotupacho, zina zonse zimachokera ku matenda oyenera.
Kuzungulira DNA kungagwiritsidwe ntchito monga chizindikiro cha matenda. Kuzungulira DNA kungagwiritsidwe ntchito poyang'anira kusintha kwa khansa pa nthawi. Mwachitsanzo, kafukufuku wina adawonetsa kuti zaka ziwiri zomwe zimakhala ndi moyo wathanzi kwa odwala omwe ali ndi khansa yosaoneka bwino (ie, chiwerengero cha odwala omwe ali ndi moyo zaka zingapo pambuyo pozindikira kuti ali ndi khansara yaikulu) ndipo kusintha kwa KRAS hotspot kunali 100% mwa iwo opanda umboni wa DNA yozungulira yofanana. Komanso, n'zotheka kuti posachedwa, kuyendetsa DNA kungagwiritsidwe ntchito poyang'anira zilonda zam'tsogolo.
Kuzungulira DNA kungagwiritsidwenso ntchito kuyang'anitsitsa kuyankhidwa kwa mankhwala. Chifukwa chakuti DNA imafotokoza bwino momwe maselo amapezera, DNAyi imakhala ndi DNA yodalirika, yomwe ingagwiritsidwe ntchito m'malo mofufuza DNA yochokera m'matumbo okha.
Tsopano tiyeni tiwone zitsanzo zenizeni za chiwonetsero cha madzi.
Guardant360
Thanzi Labwino linayambitsa mayeso omwe amagwiritsira ntchito mbadwo wotsatizana kuti azitha kusintha DNA chifukwa cha kusintha kwa maselo komanso kusintha kwa magetsi kwa majeremusi okwana 73. Health Care anasindikiza kafukufuku wofotokoza momwe ntchito yogwiritsira ntchito madzi imagwiritsiridwa ntchito pang'onopang'ono. Phunziroli linagwiritsa ntchito zitsanzo za magazi kuchokera kwa odwala 15,000 omwe ali ndi mitundu yosiyanasiyana ya matenda 50.
Kawirikawiri, zotsatira za kuyesa kwachidziwitso kwa madzi ndi zofanana ndi majini omwe amapezeka mu ziphuphu zamagazi.
Malinga ndi NIH:
Guardant360 inapeza kusintha kofanana komweku m'kati mwa majeremusi okhudzana ndi khansa monga EGFR, BRAF, KRAS , ndi PIK3CA pafupipafupi zofanana ndi zomwe zakhala zikupezeka mu zitsanzo zokhudzana ndi chifuwa, zomwe zikugwirizana ndi 94% mpaka 99%.
Komanso, malinga ndi NIH, ofufuza adafotokoza izi:
Pachigawo chachiwiri cha phunziroli, ochita kafukufuku anayezetsa odwala pafupifupi 400-ambiri omwe anali ndi mapapu kapena khansara-omwe anali ndi ctDNA ya magazi ndi minofu ya DNA yomwe ilipo ndipo amayerekeza ndi kusintha kwa maonekedwe. Kutsimikizirika kwathunthu kwa madzi amadzimadziwa poyerekeza ndi zotsatira kuchokera ku zowonongeka kwa chiphuphu chinali 87%. Kulondola kunakula mpaka 98 peresenti pamene magazi ndi zithupsa zinasonkhanitsidwa mkati mwa miyezi isanu ndi umodzi.
Guardant360 inali yolondola ngakhale kuti magulu ozungulira DNA m'magazi anali otsika. Nthaŵi zambiri, kuyendetsa DNA yotupa kumapanga 0,4 peresenti ya DNA m'magazi.
Kwenikweni, pogwiritsa ntchito madzi osokoneza bongo, ofufuza a Walonda adatha kudziwa zolemba zotupa zomwe zingawathandize madokotala 67 peresenti ya odwala. Odwalawa anali oyenera kulandira mankhwala a FDA komanso mankhwala othandizira.
ctDNA ndi khansa ya m'mimba
Mu 2016, a FDA adavomereza mayeso a mtundu wa cobas EGFR Mutation kuti agwiritsidwe ntchito kuti azindikire kusintha kwa EGFR mu DNA yozungulira ya odwala khansa ya m'mapapo. Chiyesochi chinali choyamba chovomerezeka cha FDA ndipo anazindikira odwala omwe angakhale odwala kuchipatala pogwiritsa ntchito erlotinib (Tarceva), afatinib (Gilotrif), ndi gefitinib (Iressa) monga chithandizo choyamba, komanso osimeritinib (Tagrisso) monga mankhwala achiwiri. Njira zochiritsirazi zimayambitsa maselo a khansa ndi kusintha kwa EGFR .
Chofunika kwambiri, chifukwa cha chiwerengero chachikulu cha zotsatira zoipa zabodza, a FDA amalimbikitsa kuti chinyama cha chiopsezochi chichotsedwe kuchokera kwa wodwalayo yemwe ali ndi vuto loipa la madzi.
ctDNA ndi khansa ya chiwindi
Chiwerengero cha anthu akufa ndi khansa ya chiwindi chawonjezeka zaka 20 zapitazo. Pakalipano, khansa ya chiwindi ndi yachiwiri yomwe imayambitsa khansa kufa padziko lapansi. Palibe mankhwala abwino omwe angapezeke ndikuwunika chiwindi, kapena hepatocellular (HCC), khansara. Kuzungulira DNA kungakhale katswiri wabwino wa khansa ya chiwindi.
Taganizirani mawu otsatiridwawa a Lagbaa ndi olemba anzawo potsata kugwiritsa ntchito DNA kuti apeze khansa ya chiwindi:
Hypermethylation ya RASSF1A, p15, ndi p16 zakhala zikugwiritsidwa ntchito ngati zipangizo zoyambirira zogwiritsira ntchito pofufuza zomwe zimachitika kuphatikizapo odwala 50 HCC. Kulemba kwa majeremusi anayi oopsa kwambiri (APC, GSTP1, RASSF1A, ndi SFRP1) nayenso anayesedwa kuti azindikire molondola, pamene methylation ya RASSF1A inanenedwa ngati chitsimikizo chodziwika bwino. Kafukufuku wotsatira anafufuza ctDNA mwa odwala HCC pogwiritsa ntchito matekinoloje ojambulira mwamphamvu .... Zovuta kwambiri, DNA yowonetsera ziwerengero zinapezedwa muzitsulo ziwiri za HBV popanda mbiri yakale ya HCC panthawi ya kusonkhanitsa mwazi, koma amene anapanga HCC panthawi yotsatira. Zomwe anapezazi zinatsegula chitseko kuti aone momwe chiwerengero cha ctDNA chikusinthira ngati chida chowonetsera ma HCC oyambirira.
Mawu Ochokera
Zamadzimadzi zamadzimadzi ndi njira yatsopano yosinthira matenda opatsirana pogonana. Pakalipano, mankhwala enaake, omwe amapereka mafotokozedwe ambirimbiri a ma maselo, amapezeka kwa madokotala kuti amvetsetse mauthenga a majini omwe amachokera ku chidziwitso cha minofu. Palinso mitundu ina yamadzi yomwe imatha kugwiritsidwa ntchito m'malo mwa ziphuphu zamkati-pamene minofu ya minofu isapezeke.
Ndikofunika kukumbukira kuti mayesero ambiri amadzimadzi amadziwikabe pakalipano ndipo kafukufuku amafunikanso kuchitidwa mthupi mwachithandizo cha mankhwalawa.
> Zotsatira:
> Kuyesedwa kwa Magazi Kusinthika kwa Genetic mu Mamimba Kumasonyeza Lonjezo Monga Njira Yina Kugonjera Chiopsezo. NIH.
> Heitzer E, Ulz P, Geigl JB. Kutulutsa Tumor DNA monga Chiopsezo Chakumwa kwa Khansa. Clinical Chemistry. 2015; 61: 112-123. lembani: 10.1373 / clinchem.2014.222679
> Lagbaa J, Villanueva A. Zamadzimadzi zimatulutsa khansa ya chiwindi. Kupeza Mankhwala. 2015; 19 (105): 263-73.
> Zamadzimadzi Zamadzimadzi: Kugwiritsa ntchito DNA mu Magazi kuti azindikire, Tsatirani, ndi Kuchiza Khansara. NIH.
> Umetani N, et al. Kuwonjezera kwa kuchulukitsa DNA mu seramu kusiyana ndi m'magazi a m'magazi sikumayambitsidwa ndi DNA yophatikizapo panthawi yopatukana. Ann NY Acad 2006; 1075: 299-307.
> Wellstein A. Mfundo Zambiri pa Pharmacotherapy ya khansa. Mu: Brunton LL, Hilal-Dandan R, Knollmann BC. eds. Goodman & Gilman's: The Pharmacological Basis Therapeutics, 13e New York, NY: McGraw-Hill.