Isotype-specific inhibition of the phosphatidylinositol-3-kinase pathway in hematologic malignancies

OncoTargets and Therapy

Volumn 7, Issue , 2014, Pages 333-342

  Castillo, Jorge J ^a   Iyengar, Meera ^b   Kuritzky, Benjamin ^b   Bishop, Kenneth D ^b  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b RHODE ISLAND HOSPITAL   (United States)

Author keywords

Inhibitors; Leukemia; Lymphoma; Myeloma; Phosphatidylinositol 3 kinase pathway

Indexed keywords

2 (4 HYDROXYPHENYL) 4 MORPHOLINOPYRIDO[3',2':4,5]FURO[3,2 D]PYRIMIDINE; 2 (6 AMINO 9 PURINYLMETHYL) 5 METHYL 3 (2 METHYLPHENYL) 3H QUINAZOLIN 4 ONE; 2 MORPHOLINO 8 PHENYLCHROMONE; AMG 319; ARSENIC TRIOXIDE; BAG 956; BENDAMUSTINE; BGT 226; BORTEZOMIB; BUPARLISIB; DACTOLISIB; DOXORUBICIN; DUVELISIB; EVEROLIMUS; IDELALISIB; IMATINIB; ISOENZYME; LENALIDOMIDE; NILOTINIB; OFATUMUMAB; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; RAPAMYCIN; RITUXIMAB; UNCLASSIFIED DRUG; VINCRISTINE;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; BIOLOGICAL THERAPY; CANCER SURVIVAL; CARCINOGENESIS; CHRONIC LYMPHATIC LEUKEMIA; CYTOKINE RELEASE SYNDROME; DIARRHEA; DRUG BIOAVAILABILITY; DRUG ERUPTION; ENZYME INHIBITION; FEVER; FOLLICULAR LYMPHOMA; HEMATOLOGIC MALIGNANCY; HODGKIN DISEASE; HUMAN; HYPERTRANSAMINASEMIA; LARGE CELL LYMPHOMA; LEUKEMIA; LEUKEMOGENESIS; LYMPHOMA; MANTLE CELL LYMPHOMA; MYELOMA; NEUTROPENIA; NONHODGKIN LYMPHOMA; NONHUMAN; PNEUMONIA; REVIEW; THROMBOCYTOPENIA;

EID: 84895426298     PISSN: 11786930     EISSN: None     Source Type: Journal    
DOI: 10.2147/OTT.S34641     Document Type: Review

References (54)

1. Markman B, Dienstmann R, Tabernero J. Targeting the PI3K/Akt/mTOR pathway-beyond rapalogs. Oncotarget. 2010;1(7):530-543.
2. Reif K, Okkenhaug K, Sasaki T, etal. Cutting edge: differential roles for phosphoinositide 3-kinases, p110gamma and p110delta, in lymphocyte chemotaxis and homing. J Immunol. 2004;173(4):2236-2240.
3. Williams R, Berndt A, Miller S, etal. Form and flexibility in phosphoinositide 3-kinases. Biochem Soc Trans. 2009;37 Pt 4:615-626.
4. Castillo JJ, Furman M, Winer ES. CAL-101: a phosphatidylinositol-3-kinase p110-delta inhibitor for the treatment of lymphoid malignancies. Expert Opin Investig Drugs. 2012;21(1):15-22.
5. Chantry D, Vojtek A, Kashishian A, etal. p110delta, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes. J Biol Chem. 1997;272(31): 19236-19241.
6. Herman SE, Gordon AL, Wagner AJ, etal. Phosphatidylinositol 3-kinase-delta inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals. Blood. 2010;116(12):2078-2088.
7. Sujobert P, Bardet V, Cornillet-Lefebvre P, etal. Essential role for the p110delta isoform in phosphoinositide 3-kinase activation and cell proliferation in acute myeloid leukemia. Blood. 2005;106(3):1063-1066.
8. Borlado LR, Redondo C, Alvarez B, etal. Increased phosphoinositide 3-kinase activity induces a lymphoproliferative disorder and contributes to tumor generation in vivo. FASEB J. 2000;14(7):895-903.
9. Uddin S, Hussain AR, Siraj AK, etal. Role of phosphatidylinositol 3′-kinase/AKT pathway in diffuse large B-cell lymphoma survival. Blood. 2006;108(13):4178-4186.
10. Hasselblom S, Hansson U, Olsson M, etal. High immunohistochemical expression of p-AKT predicts inferior survival in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Br J Haematol. 2010;149(4):560-568.
11. Rudelius M, Pittaluga S, Nishizuka S, etal. Constitutive activation of Akt contributes to the pathogenesis and survival of mantle cell lymphoma. Blood. 2006;108(5):1668-1676.
12. Garcia-Martinez JM, Wullschleger S, Preston G, etal. Effect of PI3K-and mTOR-specific inhibitors on spontaneous B-cell follicular lymphomas in PTEN/LKB1-deficient mice. Br J Cancer. 2011;104(7):1116-1125.
13. Renne C, Willenbrock K, Martin-Subero JI, etal. High expression of several tyrosine kinases and activation of the PI3K/AKT pathway in mediastinal large B cell lymphoma reveals further similarities to Hodgkin lymphoma. Leukemia. 2007;21(4):780-787.
14. Ikeda H, Hideshima T, Fulciniti M, etal. PI3K/p110{delta} is a novel therapeutic target in multiple myeloma. Blood. 2010;116(9):1460-1468.
15. Lannutti BJ, Meadows SA, Herman SE, etal. CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood. 2011;117(2):591-594.
16. Hoellenriegel J, Meadows SA, Sivina M, etal. The phosphoinositide 3′-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood. 2011;118(13):3603-3612.
17. Herman SE, Lapalombella R, Gordon AL, etal. The role of phosphatidylinositol 3-kinase-delta in the immunomodulatory effects of lenalidomide in chronic lymphocytic leukemia. Blood. 2011;117(16): 4323-4327.
18. Chanan-Khan AA, Chitta K, Ersing N, etal. Biological effects and clinical significance of lenalidomide-induced tumour flare reaction in patients with chronic lymphocytic leukaemia: in vivo evidence of immune activation and antitumour response. Br J Haematol. 2011;155(4):457-467.
19. Meadows SA, Vega F, Kashishian A, etal. PI3Kdelta inhibitor, GS-1101 (CAL-101), attenuates pathway signaling, induces apoptosis, and overcomes signals from the microenvironment in cellular models of Hodgkin lymphoma. Blood. 2012;119(8):1897-1900.
20. Sinclair A, Metz D, Cushing T, etal. Phosphatidylinositol-3 kinase delta (PI3K{delta}) Inhibitor AMG 319 is a potent, selective and orally bioavailable small molecule inhibitor that suppresses PI3K-mediated signaling and viability in neoplastic B cells. ASH Annual Meeting Abstracts. 2011;118(21):4964.
21. Liu L, Sun B-C, Pistillo J, etal. Phosphatidylinsoitol-3 kinase delta (PI3K{delta}) inhibitor AMG 319 combined with vincristine enhances G2/M arrest and apoptotic death in neoplastic B cells. ASH Annual Meeting Abstracts. 2011;118(21):4963.
22. Billottet C, Grandage VL, Gale RE, etal. A selective inhibitor of the p110delta isoform of PI 3-kinase inhibits AML cell proliferation and survival and increases the cytotoxic effects of VP16. Oncogene. 2006;25(50):6648-6659.
23. Billottet C, Banerjee L, Vanhaesebroeck B, etal. Inhibition of class I phosphoinositide 3-kinase activity impairs proliferation and triggers apoptosis in acute promyelocytic leukemia without affecting atra-induced differentiation. Cancer Res. 2009;69(3):1027-1036.
24. Maira SM, Stauffer F, Brueggen J, etal. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther. 2008;7(7):1851-1863.
25. Chapuis N, Tamburini J, Green AS, etal. Dual inhibition of PI3K and mTORC1/2 signaling by NVP-BEZ235 as a new therapeutic strategy for acute myeloid leukemia. Clin Cancer Res. 2010;16(22):5424-5435.
26. McMillin DW, Ooi M, Delmore J, etal. Antimyeloma activity of the orally bioavailable dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235. Cancer Res. 2009;69(14): 5835-5842.
27. Bhende PM, Park SI, Lim MS, etal. The dual PI3K/mTOR inhibitor, NVP-BEZ235, is efficacious against follicular lymphoma. Leukemia. 2010;24(10):1781-1784.
28. Kim A, Park S, Lee JE, etal. The dual PI3K and mTOR inhibitor NVP-BEZ235 exhibits anti-proliferative activity and overcomes bortezomib resistance in mantle cell lymphoma cells. Leuk Res. 2012;36(7):912-920.
29. Stauffer F, Maira SM, Furet P, etal. Imidazo[4,5-c]quinolines as inhibitors of the PI3K/PKB-pathway. Bioorg Med Chem Lett. 2008;18(3): 1027-1030.
30. Weisberg E, Banerji L, Wright RD, etal. Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL-and mutant FLT3-expressing cells. Blood. 2008;111(7): 3723-3734.
31. Baumann P, Schneider L, Mandl-Weber S, etal. Simultaneous targeting of PI3K and mTOR with NVP-BGT226 is highly effective in multiple myeloma. Anticancer Drugs. 2012;23(1):131-138.
32. Kampa-Schittenhelm KM, Heinrich MC, Akmut F, etal. Cell cycle-dependent activity of the novel dual PI3K-MTORC1/2 inhibitor NVP-BGT226 in acute leukemia. Mol Cancer. 2013;12:46.
33. Knight ZA, Gonzalez B, Feldman ME, etal. A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell. 2006;125(4):733-747.
34. Park S, Chapuis N, Bardet V, etal. PI-103, a dual inhibitor of Class IA phosphatidylinositide 3-kinase and mTOR, has antileukemic activity in AML. Leukemia. 2008;22(9):1698-1706.
35. Niedermeier M, Hennessy BT, Knight ZA, etal. Isoform-selective phosphoinositide 3′-kinase inhibitors inhibit CXCR4 signaling and overcome stromal cell-mediated drug resistance in chronic lymphocytic leukemia: a novel therapeutic approach. Blood. 2009;113(22):5549-5557.
36. Glassford J, Kassen D, Quinn J, etal. Inhibition of cell cycle progression by dual phosphatidylinositol-3-kinase and mTOR blockade in cyclin D2 positive multiple myeloma bearing IgH translocations. Blood Cancer J. 2012;2(1):e50.
37. Winkler DG, Faia KL, Dinitto JP, etal. PI3K-delta and PI3K-gamma inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013;20(11):1364-1374.
38. Horwitz SM, Flinn I, Patel MR, etal. Preliminary safety and efficacy of IPI-145, a potent inhibitor of phosphoinositide-3-kinase-{delta},{gamma}, in patients with relapsed/refractory lymphoma. ASCO Meeting Abstracts. 2013;31(Suppl 15):8518.
39. Maira SM, Pecchi S, Huang A, etal. Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. Mol Cancer Ther. 2012;11(2):317-328.
40. Zang C, Eucker J, Liu H, etal. Inhibition of pan-class I phosphatidyl-inositol-3-kinase by NVP-BKM120 effectively blocks proliferation and induces cell death in diffuse large B-cell lymphoma. Leuk Lymphoma. July 25, 2013. [Epub ahead of print.]
41. Amrein L, Shawi M, Grenier J, etal. The phosphatidylinositol-3 kinase I inhibitor BKM120 induces cell death in B-chronic lymphocytic leukemia cells in vitro. Int J Cancer. 2013;133(1):247-252.
42. Rosich L, Saborit-Villarroya I, Lopez-Guerra M, etal. The phosphatidylinositol-3-kinase inhibitor NVP-BKM120 overcomes resistance signals derived from microenvironment by regulating the Akt/FoxO3a/Bim axis in chronic lymphocytic leukemia cells. Haematologica. 2013;98(11):1739-1747.
43. Zheng Y, Yang J, Qian J, etal. Novel phosphatidylinositol 3-kinase inhibitor NVP-BKM120 induces apoptosis in myeloma cells and shows synergistic anti-myeloma activity with dexamethasone. J Mol Med (Berl). 2012;90(6):695-706.
44. Brown JR, Furman RR, Flinn I, etal. Final results of a phase I study of idelalisib (GSE1101) a selective inhibitor of PI3K{delta}, in patients with relapsed or refractory CLL. ASCO Meeting Abstracts. 2013;31(Suppl 15):7003.
45. Barrientos JC, Furman RR, Leonard J, etal. Update on a phase I study of the selective PI3K{delta} inhibitor idelalisib (GS-1101) in combination with rituximab and/or bendamustine in patients with relapsed or refractory CLL. ASCO Meeting Abstracts. 2013;31(Suppl 15):7017.
46. Benson DM, Kahl BS, Furman RR, etal. Final results of a phase I study of idelalisib, a selective inhibitor of PI3K{delta}, in patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL). ASCO Meeting Abstracts. 2013;31(Suppl 15):8526.
47. Leonard J, Wagner-Johnston ND, Coutre SE, etal. Tolerability and activity of combinations of the PI3K{delta} inhibitor idelalisib (GS-1101) with rituximab and/or bendamustine in patients with previously treated, indolent non-Hodgkin lymphoma (iNHL): updated results from a phase I study. ASCO Meeting Abstracts. 2013;31(Suppl 15): 8500.
48. Spurgeon SEF, Wagner-Johnston ND, Furman RR, etal. Final results of a phase I study of idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase P110{delta} (PI3K{delta}), in patients with relapsed or refractory mantle cell lymphoma (MCL). ASCO Meeting Abstracts. 2013; 31(Suppl 15):8519.
49. Wagner-Johnston ND, De Vos S, Leonard J, etal. Preliminary results of PI3K{delta} inhibitor idelalisib (GS-1101) treatment in combination with everolimus, bortezomib, or bendamustine/rituximab in patients with previously treated mantle cell lymphoma (MCL). ASCO Meeting Abstracts. 2013;31(Suppl 15):8501.
50. O'Brien SM, Lamanna N, Kipps TJ, etal. A phase II study of the selective phosphatidylinositol 3-kinase delta (PI3K{delta}) inhibitor idelalisib (GS-1101) in combination with rituximab (R) in treatment-naive patients (pts) ≥65 years with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). ASCO Meeting Abstracts. 2013;31(Suppl 15):7005.
51. Flinn I, Kimby E, Cotter FE, etal. A phase III, randomized, controlled study evaluating the efficacy and safety of idelalisib (GS-1101) in combination with ofatumumab for previously treated chronic lymphocytic leukemia (CLL). ASCO Meeting Abstracts. 2013;31(Suppl 15): TPS7131.
52. Eradat HA, Coutre SE, Barrientos JC, etal. A phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of idelalisib (GS-1101) in combination with bendamustine and rituximab for previously treated chronic lymphocytic leukemia (CLL). ASCO Meeting Abstracts. 2013;31(Suppl 15):TPS7133.
53. Leonard J, Zinzani PL, Jurczak W, etal. A phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of idelalisib (GS-1101) in combination with rituximab for previously treated indolent non-Hodgkin lymphomas (iNHL). ASCO Meeting Abstracts. 2013;31(Suppl 15):TPS8617.
54. De Vos S, Sehn LH, Mulligan SP, etal. A phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of idelalisib (GS-1101) in combination with bendamustine and rituximab for previously treated indolent non-Hodgkin lymphomas (iNHL). ASCO Meeting Abstracts. 2013;31(Suppl 15):TPS8618.