Should individual PI3 kinase isoforms be targeted in cancer?
Should individual PI3 kinase isoforms be targeted in cancer?
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DOI：
10.1016/j.ceb.2008.12.007
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发表时间：
2009-04
影响因子：
7.5
通讯作者：
Zhao JJ
中科院分区：
文献类型：
--
作者：
Jia S;Roberts TM;Zhao JJ
PI3K信号通路的激活在常见的人类癌症中经常发现，这是由致癌rtk上游作用、PTEN丢失或激活PI3K本身突变引起的。最近的研究已经描述了p110α和p110β在细胞信号传导和肿瘤发生中的不同但重叠的功能，p110α和p110β是PI3K在常见肿瘤类型的起源组织中表达的两个主要催化亚基。在研究的大多数细胞类型中，p110α在经典的RTK信号转导中携带大部分PI3K信号，而p110β则响应gpcr。p110α和p110β在PI3K通路组分改变诱导的细胞转化中起作用。具体来说，p110α对于PIK3CA突变和/或致癌RTKs/Ras驱动的肿瘤的信号传导和生长至关重要，而p110β是介导pten缺陷肿瘤发生的主要亚型。虽然泛pi3k抑制剂目前正在临床测试中，但p110异构体特异性抑制有望成为一种治疗策略。
Activation of the PI3K signaling pathway is frequently found in common human cancers, brought about by oncogenic RTKs acting upstream, PTEN loss, or activating mutations of PI3K itself. Recent studies have delineated distinct but overlapping functions in cell signaling and tumorigenesis for p110α and p110β, the two major catalytic subunits of PI3K expressed in the tissues of origin for the common tumor types. In most cell types studied, p110α carries the majority of the PI3K signal in classic RTK signal transduction, while p110β responds to GPCRs. Both p110α and p110β function in cellular transformation induced by alterations in components of PI3K pathway. Specifically, p110α is essential for the signaling and growth of tumors driven by PIK3CA mutations and/or oncogenic RTKs/Ras, whereas p110β is the major isoform in mediating PTEN-deficient tumorigenesis. While pan-PI3K inhibitors are currently being tested in the clinic, p110 isoform-specific inhibition holds forth promise as a therapeutic strategy.
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有效使用 PI3K 和 MEK 抑制剂治疗突变型 Kras G12D 和 PIK3CA H1047R 小鼠肺癌。
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.0701005104
发表时间：
2007-03-27
影响因子：
11.1
作者：
Gymnopoulos, Marco;Elsliger, Marc-Andre;Vogt, Peter K.
通讯作者：
Vogt, Peter K.
影响因子：
7.3
作者：
Ciraolo E;Iezzi M;Marone R;Marengo S;Curcio C;Costa C;Azzolino O;Gonella C;Rubinetto C;Wu H;Dastrù W;Martin EL;Silengo L;Altruda F;Turco E;Lanzetti L;Musiani P;Rückle T;Rommel C;Backer JM;Forni G;Wymann MP;Hirsch E
通讯作者：
Hirsch E
磷脂酰肌醇3-激酶过度激活导致拉帕替尼的抗性，这是由mTOR/磷脂酰/磷脂酰肌醇3-激酶抑制剂NVP-BEZ235逆转的。
影响因子：
11.2
作者：
Eichhorn PJ;Gili M;Scaltriti M;Serra V;Guzman M;Nijkamp W;Beijersbergen RL;Valero V;Seoane J;Bernards R;Baselga J
通讯作者：
Baselga J
影响因子：
64.8
作者：
Chin, L.;Meyerson, M.;Aldape, K.;Bigner, D.;Mikkelsen, T.;VandenBerg, S.;Kahn, A.;Penny, R.;Ferguson, M. L.;Gerhard, D. S.;Getz, G.;Brennan, C.;Taylor, B. S.;Winckler, W.;Park, P.;Ladanyi, M.;Hoadley, K. A.;Verhaak, R. G. W.;Hayes, D. N.;Spellman, Paul T.;Absher, D.;Weir, B. A.;Ding, L.;Wheeler, D.;Lawrence, M. S.;Cibulskis, K.;Mardis, E.;Zhang, Jinghui;Wilson, R. K.;Donehower, L.;Wheeler, D. A.;Purdom, E.;Wallis, J.;Laird, P. W.;Herman, J. G.;Schuebel, K. E.;Weisenberger, D. J.;Baylin, S. B.;Schultz, N.;Yao, Jun;Wiedemeyer, R.;Weinstein, J.;Sander, C.;Gibbs, R. A.;Gray, J.;Kucherlapati, R.;Lander, E. S.;Myers, R. M.;Perou, C. M.;McLendon, Roger;Friedman, Allan;Van Meir, Erwin G;Brat, Daniel J;Mastrogianakis, Gena Marie;Olson, Jeffrey J;Lehman, Norman;Yung, W. K. Alfred;Bogler, Oliver;Berger, Mitchel;Prados, Michael;Muzny, Donna;Morgan, Margaret;Scherer, Steve;Sabo, Aniko;Nazareth, Lynn;Lewis, Lora;Hall, Otis;Zhu, Yiming;Ren, Yanru;Alvi, Omar;Yao, Jiqiang;Hawes, Alicia;Jhangiani, Shalini;Fowler, Gerald;San Lucas, Anthony;Kovar, Christie;Cree, Andrew;Dinh, Huyen;Santibanez, Jireh;Joshi, Vandita;Gonzalez-Garay, Manuel L.;Miller, Christopher A.;Milosavljevic, Aleksandar;Sougnez, Carrie;Fennell, Tim;Mahan, Scott;Wilkinson, Jane;Ziaugra, Liuda;Onofrio, Robert;Bloom, Toby;Nicol, Rob;Ardlie, Kristin;Baldwin, Jennifer;Gabriel, Stacey;Fulton, Robert S.;McLellan, Michael D.;Larson, David E.;Shi, Xiaoqi;Abbott, Rachel;Fulton, Lucinda;Chen, Ken;Koboldt, Daniel C.;Wendl, Michael C.;Meyer, Rick;Tang, Yuzhu;Lin, Ling;Osborne, John R.;Dunford-Shore, Brian H.;Miner, Tracie L.;Delehaunty, Kim;Markovic, Chris;Swift, Gary;Courtney, William;Pohl, Craig;Abbott, Scott;Hawkins, Amy;Leong, Shin;Haipek, Carrie;Schmidt, Heather;Wiechert, Maddy;Vickery, Tammi;Scott, Sacha;Dooling, David J.;Chinwalla, Asif;Weinstock, George M.;O'Kelly, Michael;Robinson, Jim;Alexe, Gabriele;Beroukhim, Rameen;Carter, Scott;Chiang, Derek;Gould, Josh;Gupta, Supriya;Korn, Josh;Mermel, Craig;Mesirov, Jill;Monti, Stefano;Nguyen, Huy;Parkin, Melissa;Reich, Michael;Stransky, Nicolas;Garraway, Levi;Golub, Todd;Protopopov, Alexei;Perna, Ilana;Aronson, Sandy;Sathiamoorthy, Narayan;Ren, Georgia;Kim, Hyunsoo;Kong, Sek Won;Xiao, Yonghong;Kohane, Isaac S.;Seidman, Jon;Cope, Leslie;Pan, Fei;Van Den Berg, David;Van Neste, Leander;Yi, Joo Mi;Li, Jun Z.;Southwick, Audrey;Brady, Shannon;Aggarwal, Amita;Chung, Tisha;Sherlock, Gavin;Brooks, James D.;Jakkula, Lakshmi R.;Lapuk, Anna V.;Marr, Henry;Dorton, Shannon;Choi, Yoon Gi;Han, Ju;Ray, Amrita;Wang, Victoria;Durinck, Steffen;Robinson, Mark;Wang, Nicholas J.;Vranizan, Karen;Peng, Vivian;Van Name, Eric;Fontenay, Gerald V.;Ngai, John;Conboy, John G.;Parvin, Bahram;Feiler, Heidi S.;Speed, Terence P.;Socci, Nicholas D.;Olshen, Adam;Lash, Alex;Reva, Boris;Antipin, Yevgeniy;Stukalov, Alexey;Gross, Benjamin;Cerami, Ethan;Wang, Wei Qing;Qin, Li-Xuan;Seshan, Venkatraman E.;Villafania, Liliana;Cavatore, Magali;Borsu, Laetitia;Viale, Agnes;Gerald, William;Topal, Michael D.;Qi, Yuan;Balu, Sai;Shi, Yan;Wu, George;Bittner, Michael;Shelton, Troy;Lenkiewicz, Elizabeth;Morris, Scott;Beasley, Debbie;Sanders, Sheri;Sfeir, Robert;Chen, Jessica;Nassau, David;Feng, Larry;Hickey, Erin;Schaefer, Carl;Madhavan, Subha;Buetow, Ken;Barker, Anna;Vockley, Joseph;Compton, Carolyn;Vaught, Jim;Fielding, Peter;Collins, Francis;Good, Peter;Guyer, Mark;Ozenberger, Brad;Peterson, Jane;Thomson, Elizabeth
通讯作者：
Thomson, Elizabeth