Uguquko lwe-Human ROS1 Fusion Gene

I-ROS1 yi-transmembrane tyrosine kinase yosapho lwe-insulin receptor. I-ROS1 fusion gene iqinisekisiwe njengenye i-gene ebalulekileyo eqhuba umhlaza wamaphaphu engengoweseli encinci. Njengommeli we-subtype entsha eyahlukileyo ye-molecular, ukwenzeka kwe-ROS1 fusion gene kwi-NSCLC Malunga ne-1% ukuya kwi-2% I-ROS1 ikakhulu idlula kwi-gene rearrangment kwi-exons yayo 32, 34, 35 kunye ne-36. Emva kokuba idityaniswe nee-gene ezifana ne-CD74, EZR, SLC34A2, kunye ne-SDC4, iya kuqhubeka nokusebenza ummandla we-ROS1 tyrosine kinase. I-ROS1 kinase engasebenzi ngendlela engaqhelekanga inokusebenzisa iindlela zokubonisa ezisezantsi ezifana ne-RAS/MAPK/ERK, PI3K/Akt/mTOR, kunye ne-JAK3/STAT3, ngaloo ndlela ithatha inxaxheba ekwandeni, ekuhlukaniseni nasekutshintsheni kweeseli ze-tumor, kwaye ibangele umhlaza. Phakathi kokuguqulwa kwe-ROS1 fusion, i-CD74-ROS1 imalunga ne-42%, i-EZR imalunga ne-15%, i-SLC34A2 imalunga ne-12%, kwaye i-SDC4 imalunga ne-7%. Izifundo zibonise ukuba indawo yokubopha i-ATP ye-catalytic domain ye-ROS1 kinase kunye nendawo yokubopha i-ATP ye-ALK kinase ine-homology efikelela kwi-77%, ngoko ke i-ALK tyrosine kinase small molecule inhibitor crizotinib kunye nezinye zinefuthe elicacileyo lokunyanga kunyango lwe-NSCLC nge-fusion mutation ye-ROS1. Ke ngoko, ukufunyanwa kwe-ROS1 fusion mutations sisiqalo nesiseko sokukhokela ukusetyenziswa kwamayeza e-crizotinib.