Ukuguqulwa Kwezakhi Zofuzo Zokuhlanganiswa Kwe-ROS1 Yabantu

I-ROS1 iyi-transmembrane tyrosine kinase yomndeni wama-insulin receptor. I-ROS1 fusion gene iqinisekiswe njengenye i-gene ebalulekile yomshayeli womdlavuza wamaphaphu ongeyona encane. Njengommeleli we-subtype entsha yama-molecule ehlukile, ukwanda kwe-ROS1 fusion gene ku-NSCLC Cishe u-1% kuya ku-2% I-ROS1 ikakhulukazi ihlelwa kabusha kwezakhi zofuzo kuma-exons ayo angu-32, 34, 35 kanye no-36. Ngemva kokuthi ihlanganiswe nezakhi zofuzo ezifana ne-CD74, EZR, SLC34A2, kanye ne-SDC4, izoqhubeka nokusebenzisa isifunda se-ROS1 tyrosine kinase. I-ROS1 kinase engasebenzi ngendlela engavamile ingasebenzisa izindlela zokubonisa izimpawu ezingezansi njenge-RAS/MAPK/ERK, PI3K/Akt/mTOR, kanye ne-JAK3/STAT3, ngaleyo ndlela ihlanganyele ekwandeni, ekuhlukaniseni nasekusabalaleni kwamaseli esimila, futhi ibangele umdlavuza. Phakathi kokuguqulwa kwe-ROS1 fusion, i-CD74-ROS1 ilinganiselwa ku-42%, i-EZR ilinganiselwa ku-15%, i-SLC34A2 ilinganiselwa ku-12%, kanti i-SDC4 ilinganiselwa ku-7%. Izifundo zibonise ukuthi indawo yokubopha i-ATP yesizinda se-catalytic se-ROS1 kinase kanye nendawo yokubopha i-ATP ye-ALK kinase inobuhlobo obufika ku-77%, ngakho-ke i-ALK tyrosine kinase small molecule inhibitor crizotinib nokunye kunomphumela osobala wokwelapha ekwelapheni i-NSCLC ngokuguqulwa kwe-fusion kwe-ROS1. Ngakho-ke, ukutholakala kokuguqulwa kwe-ROS1 fusion kuyisiqalo nesisekelo sokuqondisa ukusetshenziswa kwemithi ye-crizotinib.