Ukuguqulwa Kwezakhi Zofuzo Zomuntu ze-EML4-ALK Fusion

Le khithi isetshenziselwa ukuthola izinhlobo ezingu-12 zokuguqulwa kwezakhi zofuzo ze-EML4-ALK kumasampula eziguli zomdlavuza wamaphaphu ezingezona ezincane zabantu ngaphakathi kwe-vitro. Imiphumela yokuhlolwa ingeyereferensi yomtholampilo kuphela futhi akufanele isetshenziswe njengesisekelo sokwelashwa kweziguli ngakunye. Odokotela kufanele benze izahlulelo eziphelele ngemiphumela yokuhlolwa ngokusekelwe ezicini ezifana nesimo sesiguli, izinkomba zemithi, impendulo yokwelashwa, kanye nezinye izinkomba zokuhlolwa kwelebhu. Umdlavuza wamaphaphu uyisimila esibi esivame kakhulu emhlabeni wonke, futhi u-80% ~ 85% wamacala umdlavuza wamaphaphu ongeyona encane (i-NSCLC). Ukuhlanganiswa kwezakhi zofuzo ze-echinoderm microtubule-associated protein-like 4 (EML4) kanye ne-anaplastic lymphoma kinase (ALK) kuyithagethi entsha ku-NSCLC, i-EML4 kanye ne-ALK zitholakala ngokulandelana kubantu ama-P21 kanye nama-P23 bands ku-chromosome 2 futhi zihlukaniswe cishe ngama-base pair ayizigidi ezingu-12.7. Kutholakale okungenani izinhlobo ezingu-20 zokuhlanganiswa, phakathi kwazo okungu-12 kokuguqulwa kwe-fusion kuThebula 1, lapho i-mutant 1 (E13; A20) iyona evame kakhulu, ilandelwa yi-mutant 3a kanye ne-3b (E6; A20), ebalelwa cishe ku-33% kanye no-29% weziguli ezine-EML4-ALK fusion gene NSCLC, ngokulandelana. Ama-ALK inhibitors amelwe yi-Crizotinib yimithi ehloselwe ama-molecule amancane eyenzelwe ukuguqulwa kwe-ALK gene fusion. Ngokuvimbela umsebenzi wesifunda se-ALK tyrosine kinase, ukuvimba izindlela zayo zokubonisa ezingavamile, ngaleyo ndlela kuvimbele ukukhula kwamaseli omdlavuza, ukuze kufezwe ukwelashwa okuqondiwe kwama-tumors. Izifundo zemitholampilo zibonise ukuthi i-Crizotinib inesilinganiso esisebenzayo esingaphezu kuka-61% ezigulini ezine-EML4-ALK fusion mutations, kuyilapho ingenawo umthelela ezigulini zohlobo lwasendle. Ngakho-ke, ukutholakala kokuguqulwa kwe-EML4-ALK fusion mutation kuyisiqalo nesisekelo sokuqondisa ukusetshenziswa kwemithi ye-Crizotinib.