KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog)基因是GDP/GTP结合蛋白,比较重要的同家族基因还包括HRAS和NRAS。KRAS与GTP结合呈激活状态,与GDP结合呈关闭状态,KRAS可被生长因子或酪氨酸激酶(如EGFR)短暂活化,活化后的KRAS可以激活下游如控制细胞生成的PI3K-AKT-mTOR信号通路,以及控制细胞增殖的 RAS-RAF-MEK-ERK 信号通路,突变的KRAS即使无EGFR等激酶激活的情况下都会发生持续活化,导致细胞持续增殖最终发生癌变。KRAS突变类在多种肿瘤中被发现,最为常见的包括肺癌、胰腺癌等。
| 基因名: | KRAS |
| 别名: | C-K-RAS,CFC2,K-RAS2A,K-RAS2B,K-RAS4A,K-RAS4B,KI-RAS,KRAS1,KRAS2,NS,NS3,RALD,RASK2 |
| 基因ID: | 3845 |
| Chromosome: (GRCh37) | 12 Start: 25357723 End: 25403870 Strand: -1 |
| 药物: | 玻玛西林,玻玛西尼,阿贝西利 Adoptive T-cell Transfer 阿法替尼 司美替尼 ARS-1620 ARS-853 阿特珠单抗,阿替利珠单抗 AZD5438 AZD8186 瑞法替尼,瑞美替尼 贝伐单抗,贝伐珠单抗 Dactolisib 比美替尼、贝美替尼 BMS-754807 卡铂 西妥昔单抗 Chemotherapy 顺铂 考比替尼,卡比替尼 克唑替尼 达拉非尼 达沙替尼 Decitabine 多西他赛 EGFR Inhibitor 康奈非尼,恩考芬尼 厄洛替尼 反法尼基硫代水杨酸 Fluorouracil FOLFOX4方案 G-573 GDC-0623 吉非替尼 吉西他滨 GO-203-2C IMO 伊立替康 伊沙佐米 亚叶酸钙 玻玛西林,玻玛西尼,阿贝西利 MEK Inhibitor 马法兰,米尔法兰 MK-2206 2HCl 纳武单抗,纳武利尤单抗 奥沙利铂 Oxaliplatin (JAN/USAN/INN) 紫杉醇 哌柏西利/帕博西尼/帕博西林 帕尼单抗 PD0325901 哌柏西利/帕博西尼/帕博西林 派姆单抗,帕博利珠单抗 培美曲塞 PI103 PI3K Inhibitor R1507 RAF265 瑞法替尼,瑞美替尼 瑞戈非尼 地磷莫司 RO4987655 沙利雷塞 SCH772984 司美替尼 Small Molecule Inhibitor 索拉非尼 舒尼替尼 替西罗莫司/坦西莫司 曲美替尼 维莫非尼,威罗菲尼 |
虽然Kras G12区域是广泛研究的癌症复发区域,但其对临床作用的影响仍在积极讨论中。通常与其他驱动因素(egfr和alk)为野生型的肿瘤相关,这种突变患者的预后似乎比结直肠癌和胰腺癌患者的kras野生型队列更差,但这一假设需要进一步验证。这种突变,连同影响邻近的G13位置的突变,在用第一代tki(如吉非替尼)治疗时,可能导致反应性较低的肿瘤。NCCN大肠癌指南中建议,靶向治疗西妥昔单抗和帕尼图单抗只能用于野生型KRA。然而,西妥昔单抗治疗显示,在一个有g12d突变的结直肠患者队列中延长了生存期。总的来说,大多数临床情况下对Kras突变的解释还没有决定。
While the KRAS G12 region is a widely studied recurrent region in cancer, its impact on clinical action is still actively debated. Often associated with tumors that are wild-type for other drivers (EGFR and ALK specifically), the prognosis for patients with this mutation seems to be worse than the KRAS wild-type cohort in patients with colorectal and pancreatic cancer, however this hypothesis is in need of further validation. This mutation, along with the mutations affecting the neighboring G13 position, may result in a less responsive tumor when treated with first-generation TKI's like gefitinib. The NCCN guidelines for colorectal cancer contain recommendations that the targeted therapies cetuximab and panitumumab should only be used in the context of wild type KRAS. However, cetuximab treatment was shown to extend survival in a single cohort of colorectal patients with G12D mutations. Overall, the interpretation for KRAS mutations in most clinical scenarios is still undecided.
| Chr. | Start | Stop | Ref. s | Var. Bases |
| 12 | 25398284 | 25398284 | C | T |
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