PI3K isoform-selective inhibitors: Next-generation targeted cancer therapies

Acta Pharmacologica Sinica

Volumn 36, Issue 10, 2015, Pages 1170-1176

  Wang, Xiang ^a   Ding, Jian ^a   Meng, Ling Hua ^a  

^a SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

Author keywords

biomarker; CAL101; isoform selective inhibitor; PI3K isoforms; precise cancer therapy

Indexed keywords

PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE ALPHA INHIBITOR; PHOSPHATIDYLINOSITOL 3 KINASE DELTA INHIBITOR; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; IDELALISIB; ISOPROTEIN; PROTEIN KINASE INHIBITOR; PURINE DERIVATIVE; QUINAZOLINONE DERIVATIVE;

CANCER CHEMOTHERAPY; HUMAN; MALIGNANT NEOPLASTIC DISEASE; MOLECULARLY TARGETED THERAPY; REVIEW; ANIMAL; ANTAGONISTS AND INHIBITORS; ENZYMOLOGY; METABOLISM; NEOPLASMS; PROCEDURES;

ANIMALS; ANTINEOPLASTIC AGENTS; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASMS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN ISOFORMS; PROTEIN KINASE INHIBITORS; PURINES; QUINAZOLINONES;

EID: 84943271871     PISSN: 16714083     EISSN: 17457254     Source Type: Journal    
DOI: 10.1038/aps.2015.71     Document Type: Review

References (39)

1. Vanhaesebroeck B, Guillermet-Guibert J, Graupera M, Bilanges B. The emerging mechanisms of isoform-specific PI3K signalling. Nat Rev Mol Cell Biol 2010; 11: 329-41.
2. Rudd ML, Price JC, Fogoros S, Godwin AK, Sgroi DC, Merino MJ, et al. A unique spectrum of somatic PIK3CA (p110alpha) mutations within primary endometrial carcinomas. Clin Cancer Res 2011; 17: 1331-40.
3. Cheung LW, Yu S, Zhang D, Li J, Ng PK, Panupinthu N, et al. Naturally occurring neomorphic PIK3R1 mutations activate the MAPK pathway, dictating therapeutic response to MAPK pathway inhibitors. Cancer Cell 2014; 26: 479-94.
4. Rodon J, Dienstmann R, Serra V, Tabernero J. Development of PI3K inhibitors: lessons learned from early clinical trials. Nat Rev Clin Oncol 2013; 10: 143-53.
5. Jamieson S, Flanagan JU, Kolekar S, Buchanan C, Kendall JD, Lee WJ, et al. A drug targeting only p110alpha can block phosphoinositide 3-kinase signalling and tumour growth in certain cell types. Biochem J 2011; 438: 53-62.
6. Ana M. Gonzalez-Angulo DJ, Guillem A, Jan HM S, Burris HA, Berlin J, et al. Safety, pharmacokinetics, and preliminary activity of the ?-specific PI3K inhibitor BYL719: Results from the first-in-human study. J Clin Oncol 2013; 31: abstr 2531.
7. Liu JL, Gao GR, Zhang X, Cao SF, Guo CL, Wang X, et al. DW09849, a selective phosphatidylinositol 3-kinase (PI3K) inhibitor, prevents PI3K signaling and preferentially inhibits proliferation of cells containing the oncogenic mutation p110alpha (H1047R). J Pharmacol Exp Ther 2014; 348: 432-41.
8. Gobin B, Huin MB, Lamoureux F, Ory B, Charrier C, Lanel R, et al. BYL719, a new alpha-specific PI3K inhibitor: single administration and in combination with conventional chemotherapy for the treatment of osteosarcoma. Int J Cancer 2015; 136: 784-96.
9. Castellano E, Sheridan C, Thin MZ, Nye E, Spencer-Dene B, Diefenbacher ME, et al. Requirement for interaction of PI3-kinase p110alpha with RAS in lung tumor maintenance. Cancer Cell 2013; 24: 617-30.
10. Gritsman K, Yuzugullu H, Von T, Yan H, Clayton L, Fritsch C, et al. Hematopoiesis and RAS-driven myeloid leukemia differentially require PI3K isoform p110alpha. J Clin Invest 2014; 124: 1794-809.
11. Yea SS, So L, Mallya S, Lee J, Rajasekaran K, Malarkannan S, et al. Effects of novel isoform-selective phosphoinositide 3-kinase inhibitors on natural killer cell function. PLoS One 2014; 9: e99486.
12. Ogino S, Galon J, Fuchs CS, Dranoff G. Cancer immunology-analysis of host and tumor factors for personalized medicine. Nat Rev Clin Oncol 2011; 8: 711-9.
13. Fritsch C, Huang A, Chatenay-Rivauday C, Schnell C, Reddy A, Liu M, et al. Characterization of the novel and specific PI3Kalpha inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther 2014; 13: 1117-29.
14. Juric D, Castel P, Griffith M, Griffith OL, Won HH, Ellis H, et al. Convergent loss of PTEN leads to clinical resistance to a PI(3)Kalpha inhibitor. Nature 2015; 518: 240-4.
15. Wang X, Li JP, Yang Y, Ding J, Meng LH. A pharmacological model reveals biased dependency on PI3K isoforms for tumor cell growth. Acta Pharmacol Sin 2013; 34: 1201-7.
16. Ikeda H, Hideshima T, Fulciniti M, Perrone G, Miura N, Yasui H, et al. PI3K/p110{delta} is a novel therapeutic target in multiple myeloma. Blood 2010; 116: 1460-8.
17. Somoza JR, Koditek D, Villasenor AG, Novikov N, Wong MH, Liclican A, et al. Structural, biochemical, and biophysical characterization of idelalisib binding to phosphoinositide 3-Kinase delta. J Biol Chem 2015; 290: 8439-46.
18. Berndt A, Miller S, Williams O, Le DD, Houseman BT, Pacold JI, et al. The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors. Nat Chem Biol 2010; 6: 117-24.
19. Wang X, Zhang X, Li BS, Zhai X, Yang Z, Ding LX, et al. Simultaneous targeting of PI3Kdelta and a PI3Kdelta-dependent MEK1/2-Erk1/2 pathway for therapy in pediatric B-cell acute lymphoblastic leukemia. Oncotarget 2014; 5: 10732-44.
20. Wei M, Wang X, Song Z, Jiao M, Ding J, Meng LH, et al. Targeting PI3Kdelta: emerging therapy for chronic lymphocytic leukemia and beyond. Med Res Rev 2015; 35: 720-52.
21. Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med 2014; 370: 997-1007.
22. Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, et al. PI3Kdelta inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med 2014; 370: 1008-18.
23. Shugg RP, Thomson A, Tanabe N, Kashishian A, Steiner BH, Puri KD, et al. Effects of isoform-selective phosphatidylinositol 3-kinase inhibitors on osteoclasts: actions on cytoskeletal organization, survival, and resorption. J Biol Chem 2013; 288: 35346-57.
24. Lannutti BJ, Meadows SA, Herman SE, Kashishian A, Steiner B, Johnson AJ, et al. 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: 591-4.
25. Herman SE, Gordon AL, Wagner AJ, Heerema NA, Zhao W, Flynn JM, et al. 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: 2078-88.
26. Hoellenriegel J, Meadows SA, Sivina M, Wierda WG, Kantarjian H, Keating MJ, et al. The phosphoinositide 3'-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood 2011; 118: 3603-12.
27. Iyengar S, Clear A, Bodor C, Maharaj L, Lee A, Calaminici M, et al. P110alpha-mediated constitutive PI3K signaling limits the efficacy of p110delta-selective inhibition in mantle cell lymphoma, particularly with multiple relapse. Blood 2013; 121: 2274-84.
28. Ramadani F, Bolland DJ, Garcon F, Emery JL, Vanhaesebroeck B, Corcoran AE, et al. The PI3K isoforms p110alpha and p110delta are essential for pre-B cell receptor signaling and B cell development. Sci Signal 2010; 3, 60.
29. Ali K, Soond DR, Pineiro R, Hagemann T, Pearce W, Lim EL, et al. Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer. Nature 2014; 510: 407-11.
30. Ni J, Liu Q, Xie S, Carlson C, Von T, Vogel K, et al. Functional characterization of an isoform-selective inhibitor of PI3K-p110beta as a potential anticancer agent. Cancer Discov 2012; 2: 425-33.
31. Certal V, Carry JC, Halley F, Virone-Oddos A, Thompson F, Filoche-Romme B, et al. Discovery and optimization of pyrimidone indoline amide PI3Kbeta inhibitors for the treatment of phosphatase and tensin homologue (PTEN)-deficient cancers. J Med Chem 2014; 57: 903-20.
32. Schwartz S, Wongvipat J, Trigwell CB, Hancox U, Carver BS, Rodrik-Outmezguine V, et al. Feedback suppression of PI3Kalpha signaling in PTEN-mutated tumors is relieved by selective inhibition of PI3Kbeta. Cancer Cell 2015; 27: 109-22.
33. Luk SK, Piekorz RP, Nurnberg B, Tony To SS. The catalytic phosphoinositol 3-kinase isoform p110delta is required for glioma cell migration and invasion. Eur J Cancer 2012; 48: 149-57.
34. Weigelt B, Warne PH, Lambros MB, Reis-Filho JS, Downward J. PI3K pathway dependencies in endometrioid endometrial cancer cell lines. Clin Cancer Res 2013; 19: 3533-44.
35. Hirsch DS, Shen Y, Dokmanovic M, Wu WJ. 60c-Src phosphorylates and activates vacuolar protein sorting 34 to mediate cellular transformation. Cancer Res 2010; 70: 5974-83.
36. Ronan B, Flamand O, Vescovi L, Dureuil C, Durand L, Fassy F, et al. A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nat Chem Biol 2014; 10: 1013-9.
37. Liu N, Rowley BR, Bull CO, Schneider C, Haegebarth A, Schatz CA, et al. BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110alpha and p110delta activities in tumor cell lines and xenograft models. Mol Cancer Ther 2013; 12: 2319-30.
38. Barlaam B, Cosulich S, Degorce S, Fitzek M, Green S, Hancox U, et al. Discovery of (R)-8-(1-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chrom ene-6-carboxamide (AZD8186): a potent and selective inhibitor of PI3Kbeta and PI3Kdelta for the treatment of PTEN-deficient cancers. J Med Chem 2015; 58: 943-62.
39. Ndubaku CO, Heffron TP, Staben ST, Baumgardner M, Blaquiere N, Bradley E, et al. Discovery of 2-{3-[2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl]-1H-pyrazol-1-yl}-2-methylpropanamide (GDC-0032): a beta-sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity. J Med Chem 2013; 56: 4597-610.