[2]Nagashima T,et al.Novel KRAS G12D degrader ASP3082 demonstrates in vivo, dose-dependent KRAS degradation, KRAS pathway inhibition, and antitumor efficacy in multiple KRAS G12D-mutated cancer models[J]. Cancer Research...
然而RAS下游与多种效应信号途径，靶向哪种路径以及是否需同时抑制多种下游蛋白仍是关健问题。引起最大关注的两种pathway是RAF-MEK-ERK促分裂蛋白激酶（MAPK）信号通路和PI3K-AKT-mTOR信号通路。已经批准的第一代RAF抑制剂（vemurafenib和dabrafenib）用于治疗BRAF突变黑色素瘤(Danysh et al. 2016; Facchinetti et al. ...
Fruman D A, Chiu H Y, Hopkins B D, et al. The PI3K pathway inhuman disease[J]. Cell, 2017, 170(4): 605-635. Vara J A F, Casado E, de Castro J, et al. PI3K/Akt signallingpathway and cancer[J]. Cancer Treat Rev, 2...
Targeting the KRAS pathway in non-small cell lung cancer. Oncologist 2016; 21: 1450-1460.Tomasini P, Walia P, Labbe C, Jao K, Leighl NB (2016) Targeting the KRAS Pathway in Non-Small Cell Lung Cancer. Oncologist 21:1450-1460. Link: https://goo.gl/yzI...
https://www.targetmol.cn/pathway/protac 参考文献：[1] Ostrem JM, Peters U, Sos ML, Wells JA, Shokat KM. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature. 2013;503(7477):548-551. doi:10.1038/nature12796 [2] Skoulidis F, Li BT, Dy GK, ...
Drosten M, Barbacid M. Targeting the MAPK pathway in KRAS-driven tumors. Cancer Cell 37(4), 543–550 (2020). Buscail L, Bournet B, Cordelier P. Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer. Nat. Rev.Gastroenterol. Hepatol. 17(3), 153–168 ...
Jabarkheel R, Li L, Frankfurter M, Zhang DY, Gajjar A, Muhammad N, Srinivasan VM, Burkhardt J-K and Kahn M (2024) Untangling sporadic brain arteriovenous malformations: towards targeting the KRAS/MAPK pathway. Front. Surg. 11:1504612. doi: 10.3389/fsurg.2024.1504612...
Jabarkheel R, Li L, Frankfurter M, Zhang DY, Gajjar A, Muhammad N, Srinivasan VM, Burkhardt J-K and Kahn M (2024) Untangling sporadic brain arteriovenous malformations: towards targeting the KRAS/MAPK pathway. Front. Surg. 11:1504612. doi: 10.3389/fsurg.2024.1504612...
https://www.targetmol.cn/pathway/protac 参考文献：[1] Ian A. Prior, Fiona E. Hood, James L. Hartley; The Frequency of Ras Mutations in Cancer. Cancer Res 15 July 2020; 80 (14): 2969–2974. https://doi.org/10.1158/0008-5472.CAN-19-3682 [2] Punekar, S.R., Velcheti, V., ...
3.Drosten M, Barbacid M. Targeting the MAPK pathway in KRAS-driven tumors. Cancer Cell 37(4), 543–550 (2020). 4. Buscail L, Bournet B, Cordelier P. Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer. Nat. Rev.Gastroenterol. Hepatol. 17(3), 153...