Phosphoinositide 3-kinase inhibitors in lymphoma

被引:34
作者
Curran, Emily [1 ]
Smith, Sonali M. [1 ]
机构
[1] Univ Chicago, Sect Hematol Oncol, Dept Med, Chicago, IL 60637 USA
关键词
chronic lymphocytic leukemia; indolent non-Hodgkin lymphoma; mantle cell lymphoma; phosphoinositide 3-kinase inhibitors; CHRONIC LYMPHOCYTIC-LEUKEMIA; MANTLE CELL LYMPHOMA; B-CELL; PHOSPHATIDYLINOSITOL-3-KINASE INHIBITOR; JAK/STAT PATHWAYS; ANTIGEN RECEPTOR; HUMAN CANCERS; P110; DELTA; P110-DELTA; SURVIVAL;
D O I
10.1097/CCO.0000000000000113
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose of review The phosphoinositide 3-kinase (PI3K) pathway, with downstream targets including Akt and mammalian target of rapamycin, has been implicated in numerous human cancers, including hematologic malignancies and lymphomas. The development and refinement of PI3K inhibitors directed toward this pathway show promising clinical efficacy. This review will discuss the emerging body of clinical data in lymphoid malignancies and present future directions for research utilizing these inhibitors. Recent findings The PI3K delta inhibitor, idelalisib, has been most widely studied in lymphoma, and has shown promising results both as a single agent and in combination with other therapies. IPI-145, a dual inhibitor of PI3Kd and PI3K gamma, has also shown efficacy and several clinical trials are underway. Other PI3K inhibitors are in active development, with several entering early phase clinical trials. Summary The PI3K pathway appears to be important in lymphoma and targeting this pathway shows promising clinical efficacy.
引用
收藏
页码:469 / 475
页数:7
相关论文
共 46 条
[1]  
Barrientos JC, 2013, UPDATE PHASE 1 STUDY
[2]   Survival of leukemic B cells promoted by engagement of the antigen receptor [J].
Bernal, A ;
Pastore, RD ;
Asgary, Z ;
Keller, SA ;
Cesarman, E ;
Liou, HC ;
Schattner, EJ .
BLOOD, 2001, 98 (10) :3050-3057
[3]  
Brown J.R., 2013, FINAL RESULTS PHASE
[4]   Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia [J].
Brown, Jennifer R. ;
Byrd, John C. ;
Coutre, Steven E. ;
Benson, Don M. ;
Flinn, Ian W. ;
Wagner-Johnston, Nina D. ;
Spurgeon, Stephen E. ;
Kahl, Brad S. ;
Bello, Celeste ;
Webb, Heather K. ;
Johnson, Dave M. ;
Peterman, Sissy ;
Li, Daniel ;
Jahn, Thomas M. ;
Lannutti, Brian J. ;
Ulrich, Roger G. ;
Yu, Albert S. ;
Miller, Langdon L. ;
Furman, Richard R. .
BLOOD, 2014, 123 (22) :3390-3397
[5]   p110 delta, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes [J].
Chantry, D ;
Vojtek, A ;
Kashishian, A ;
Holtzman, DA ;
Wood, C ;
Gray, PW ;
Cooper, JA ;
Hoekstra, MF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (31) :19236-19241
[6]   The PI3K Pathway As Drug Target in Human Cancer [J].
Courtney, Kevin D. ;
Corcoran, Ryan B. ;
Engelman, Jeffrey A. .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (06) :1075-1083
[7]  
Coutre S, 2011, PHASE 1 STUDY CAL 10
[8]  
Coutre S, 2012, COMBINATIONS SELECTI
[9]   Distinct functional significance of Akt and mTOR constitutive activation in mantle cell lymphoma [J].
Dal Col, Jessica ;
Zancai, Paola ;
Terrin, Liliana ;
Guidoboni, Massimo ;
Ponzoni, Maurilio ;
Pavan, Alessandro ;
Spina, Michele ;
Bergamin, Stefano ;
Rizzo, Silvana ;
Tirelli, Umberto ;
De Rossi, Anita ;
Doglioni, Claudio ;
Dolcetti, Riccardo .
BLOOD, 2008, 111 (10) :5142-5151
[10]   Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma [J].
Davis, R. Eric ;
Ngo, Vu N. ;
Lenz, Georg ;
Tolar, Pavel ;
Young, Ryan M. ;
Romesser, Paul B. ;
Kohlhammer, Holger ;
Lamy, Laurence ;
Zhao, Hong ;
Yang, Yandan ;
Xu, Weihong ;
Shaffer, Arthur L. ;
Wright, George ;
Xiao, Wenming ;
Powell, John ;
Jiang, Jian-Kang ;
Thomas, Craig J. ;
Rosenwald, Andreas ;
Ott, German ;
Muller-Hermelink, Hans Konrad ;
Gascoyne, Randy D. ;
Connors, Joseph M. ;
Johnson, Nathalie A. ;
Rimsza, Lisa M. ;
Campo, Elias ;
Jaffe, Elaine S. ;
Wilson, Wyndham H. ;
Delabie, Jan ;
Smeland, Erlend B. ;
Fisher, Richard I. ;
Braziel, Rita M. ;
Tubbs, Raymond R. ;
Cook, J. R. ;
Weisenburger, Dennis D. ;
Chan, Wing C. ;
Pierce, Susan K. ;
Staudt, Louis M. .
NATURE, 2010, 463 (7277) :88-U97