title: The biology behind PI3K inhibition in chronic lymphocytic leukaemia.
abstract: Phosphoinositide 3'-kinase (PI3K) is a key component of both chronic active and tonic B-cell receptor-signalling pathways. As such, PI3K inhibitors have emerged as promising therapeutic agents for diverse lymphoid malignancies, particularly chronic lymphocytic leukaemia. Multiple in vitro experiments and clinical trials have shown efficacy of these agents across all prognostic subgroups with a favourable toxicity profile. Moreover, in vitro studies suggest that combinations with monoclonal antibodies and/or other immune strategies could enhance the effect of PI3K inhibition.
authors: Hospital Clínic, Department of Haematology Calle Villarroel, 170 08036 Barcelona, Spain.
authors: Valentín
authors: V
authors: Ortiz-Maldonado
authors: Hospital Clínic, Department of Medical Oncology Calle Villarroel, 170 08036 Barcelona, Spain.
authors: Marcial
authors: M
authors: García-Morillo
authors: Hospital Clínic, Department of Haematology Calle Villarroel, 170 08036 Barcelona, Spain.
authors: Julio
authors: J
authors: Delgado
keywords: BCR; CLL; PI3K
references: Lancet Oncol. 2014 Sep;15(10):1090-9
references: 25150798
references: J Exp Med. 2007 Apr 16;204(4):759-69
references: 17420266
references: Sci Signal. 2011 Oct 18;4(195):re2
references: 22009150
references: Nature. 2012 Oct 4;490(7418):116-20
references: 22885699
references: Nature. 2011 Jun 05;475(7354):101-5
references: 21642962
references: N Engl J Med. 2012 Feb 9;366(6):520-9
references: 22149876
references: Blood. 2011 Apr 21;117(16):4323-7
references: 21378270
references: Blood. 2011 Jan 13;117(2):563-74
references: 20940416
references: Nat Rev Drug Discov. 2014 Feb;13(2):140-56
references: 24481312
references: J Clin Oncol. 2009 Aug 10;27(23):3822-9
references: 19581539
references: Blood. 1998 Oct 15;92(8):2871-8
references: 9763572
references: Cancer Discov. 2013 Jul;3(7):761-9
references: 23619167
references: Blood. 2014 Mar 20;123(12):1957-60
references: 24652965
references: Nat Rev Immunol. 2013 Aug;13(8):578-91
references: 23883968
references: N Engl J Med. 2014 Mar 13;370(11):1008-18
references: 24450858
references: Annu Rev Immunol. 2004;22:563-98
references: 15032589
references: Blood. 2014 May 1;123(18):2783-90
references: 24615780
references: Oncogene. 1998 Jul 23;17(3):313-25
references: 9690513
references: Haematologica. 2010 Sep;95(9):1526-33
references: 20421272
references: Mol Immunol. 2004 Jul;41(6-7):599-613
references: 15219998
references: J Clin Oncol. 2014 Mar 20;32(9):897-904
references: 24516016
references: PLoS One. 2013 Dec 23;8(12):e83830
references: 24376763
references: Immunol Rev. 2000 Aug;176:30-46
references: 11043766
references: Cell. 2009 Oct 30;139(3):573-86
references: 19879843
references: J Biol Chem. 2004 Jan 9;279(2):1010-9
references: 14581487
references: Nat Rev Immunol. 2007 Aug;7(8):633-43
references: 17641666
references: Mol Cancer Ther. 2013 Oct;12 (10 ):2031-42
references: 23873847
references: N Engl J Med. 2013 Jul 4;369(1):32-42
references: 23782158
references: Blood. 2008 Jun 15;111(12):5446-56
references: 18216293
references: Cell. 2000 Jan 7;100(1):57-70
references: 10647931
references: Nat Rev Drug Discov. 2013 Mar;12(3):229-43
references: 23449308
references: N Engl J Med. 2000 Dec 14;343(24):1750-7
references: 11114313
references: Blood. 2007 Aug 15;110(4):1191-8
references: 17488877
references: Nat Genet. 2011 Dec 11;44(1):47-52
references: 22158541
references: Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11381-6
references: 20534549
references: J Clin Oncol. 2010 Apr 1;28(10 ):1749-55
references: 20194866
references: N Engl J Med. 2011 Aug 25;365(8):725-33
references: 21830940
references: N Engl J Med. 2007 Feb 15;356(7):741-2
references: 17301308
references: Nature. 2008 Aug 7;454(7205):776-9
references: 18594509
references: J Clin Oncol. 2014 Jul 1;32(19):2067-73
references: 24868031
references: N Engl J Med. 2007 May 31;356(22):2271-81
references: 17538086
references: Nature. 2010 Jan 7;463(7277):88-92
references: 20054396
references: Cell. 1997 Sep 19;90(6):1073-83
references: 9323135
references: Mol Cell Biol. 2002 Apr;22(8):2524-35
references: 11909947
references: Blood. 1999 Sep 15;94(6):1840-7
references: 10477712
references: N Engl J Med. 2014 Mar 20;370(12):1101-10
references: 24401022
references: Best Pract Res Clin Haematol. 2010 Mar;23(1):3-20
references: 20620967
references: Nature. 2014 Jun 19;510(7505):407-11
references: 24919154
references: Blood. 2010 Sep 23;116(12):2078-88
references: 20522708
references: J Clin Oncol. 1991 Jan;9(1):44-9
references: 1702145
references: J Clin Invest. 1998 Oct 15;102(8):1515-25
references: 9788964
references: Nature. 2000 Feb 3;403(6769):503-11
references: 10676951
references: Blood. 1999 Sep 15;94(6):1848-54
references: 10477713
references: Lancet Oncol. 2014 Jan;15(1):69-77
references: 24332512
references: Ann Hematol. 2009 Mar;88(3):221-7
references: 18704419
references: Blood. 2012 May 10;119(19):4467-75
references: 22415752
references: Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13057-62
references: 18755892
references: J Immunol. 2014 Apr 15;192(8):3958-68
references: 24634494
references: Haematologica. 2014 Jul;99(7):1138-48
references: 24986876
references: Lancet. 2010 Oct 2;376(9747):1164-74
references: 20888994
references: Curr Opin Immunol. 2011 Apr;23(2):178-83
references: 21277760
references: Nat Rev Cancer. 2005 Apr;5(4):251-62
references: 15803153
references: Blood. 2014 May 29;123(22):3390-7
references: 24615777
references: Lancet Oncol. 2014 Aug;15(9):1019-26
references: 25042202
references: Eur J Immunol. 2008 Dec;38(12):3543-8
references: 19016531
references: Blood. 1999 Oct 1;94(7):2357-64
references: 10498607
references: J Biol Chem. 2008 Nov 28;283(48):33296-303
references: 18786920
references: Clin Adv Hematol Oncol. 2014 Apr;12 (4):224-9
references: 25003352
references: Immunol Rev. 1993 Apr;132:187-206
references: 8349296
references: N Engl J Med. 2014 Mar 13;370(11):997-1007
references: 24450857
references: N Engl J Med. 2014 Jul 17;371(3):213-23
references: 24881631
references: Nat Rev Clin Oncol. 2013 Mar;10(3):143-53
references: 23400000
references: J Clin Oncol. 2012 Aug 10;30(23):2919-28
references: 22778315
references: Cell. 2004 Jun 11;117(6):787-800
references: 15186779
references: Mol Cell. 2002 Nov;10 (5):1057-69
references: 12453414
references: J Clin Oncol. 2012 Aug 10;30(23):2820-2
references: 22778323
references: Blood. 2013 Oct 10;122(15):2539-49
references: 23886836
references: J Exp Med. 2005 Nov 21;202(10):1423-31
references: 16301747
references: J Exp Med. 2007 Mar 19;204(3):633-43
references: 17353367
references: Blood. 2006 Jan 15;107(2):642-50
references: 16179367
references: Nature. 1997 Apr 24;386(6627):855-8
references: 9126747
references: EMBO J. 1994 Mar 15;13(6):1341-9
references: 8137818
references: Cancer Cell. 2012 May 15;21(5):694-708
references: 22624718
references: Cell. 2010 Apr 2;141(1):27-38
references: 20371343