Type III or allosteric kinase inhibitors for the treatment of non-small cell lung cancer

Expert Opinion on Investigational Drugs

Volumn 23, Issue 6, 2014, Pages 809-821

  Fasano, Morena ^a   Corte, Carminia Maria Della ^a   Califano, Raffaele ^b,c   Capuano, Annalisa ^a   Troiani, Teresa ^a   Martinelli, Erika ^a   Ciardiello, Fortunato ^a   Morgillo, Floriana ^a  

^a SECOND UNIVERSITY OF NAPLES   (Italy)

^b CHRISTIE HOSPITAL   (United Kingdom)

^c MANCHESTER UNIVERSITY NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

AKT; MAPK kinase; Non small cell lung cancer; Type III tyrosine kinase inhibitor

Indexed keywords

2 (2 CHLORO 4 IODOANILINO) N CYCLOPROPYLMETHOXY 3,4 DIFLUOROBENZAMIDE; 3,4 DIFLUORO 2 (2 FLUORO 4 IODOANILINO) N (2 HYDROXYETHOXY) 5 [(3 OXO 1,2 OXAZINAN 2 YL)METHYL]BENZAMIDE; 8 [4 (1 AMINOCYCLOBUTYL)PHENYL] 9 PHENYL 1,2,4 TRIAZOLO[3,4 F][1,6]NAPHTHYRIDIN 3(2H) ONE; ANTINEOPLASTIC AGENT; BINIMETINIB; COBIMETINIB; DOCETAXEL; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; N (2,3 DIHYDROXYPROPOXY) 3,4 DIFLUORO 2 (2 FLUORO 4 IODOANILINO)BENZAMIDE; PIMASERTIB; PLACEBO; PROTEIN KINASE B INHIBITOR; PROTEIN TYROSINE KINASE INHIBITOR; REFAMETINIB; SELUMETINIB; TAK 733; TRAMETINIB; UNCLASSIFIED DRUG; WX 554; ADENOSINE TRIPHOSPHATE; PROTEIN KINASE INHIBITOR;

ADVANCED CANCER; ANTINEOPLASTIC ACTIVITY; BINDING SITE; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; DRUG BIOAVAILABILITY; ENZYME PHOSPHORYLATION; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LUNG ADENOCARCINOMA; LUNG NON SMALL CELL CANCER; OVARY CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); RETINA VEIN OCCLUSION; REVIEW; ALLOSTERISM; ANIMAL; CARCINOMA, NON-SMALL-CELL LUNG; CLINICAL TRIAL (TOPIC); DOUBLE BLIND PROCEDURE; DRUG SCREENING; LUNG NEOPLASMS; METABOLISM; PHYSIOLOGY; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL (TOPIC);

ADENOSINE TRIPHOSPHATE; ALLOSTERIC REGULATION; ANIMALS; CARCINOMA, NON-SMALL-CELL LUNG; CLINICAL TRIALS AS TOPIC; DOUBLE-BLIND METHOD; DRUG EVALUATION, PRECLINICAL; HUMANS; LUNG NEOPLASMS; PROSPECTIVE STUDIES; PROTEIN KINASE INHIBITORS; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84900807915     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2014.902934     Document Type: Review

References (66)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics 2012. CA Cancer J Clin 2012;62:10-29
2. Savas P, Hughes B, Solomon B. Targeted therapy in lung cancer: IPASS and beyond, keeping abreast of the explosion of targeted therapies for lung cancer. J Thorac Dis 2013;5(Suppl 5):S579-92
3. Weinstein IB, Joe A. Oncogene addiction. Cancer Res 2008;68:3077-80
4. Kaelin WG Jr. The concept of synthetic lethality in the context of anticancer therapy. Nat Rev Cancer 2005;5:689-98
5. Kerbel RS. Tumor angiogenesis. N Engl J Med 2008;358:2039-49
6. Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005;2:e73
7. Liu Y, Gray NS. Rational design of inhibitors that bind to inactive kinase conformations. Nat Chem Biol 2006;2:358-64
8. Blanc J, Geney R, Menet C. Type II kinase inhibitors: an opportunity in cancer for rational design. Anticancer Agents Med Chem 2013;13:731-47
9. Garuti L, Roberti M, Bottegoni G. Non-ATP competitive protein kinase inhibitors. Curr Med Chem 2010;17:2804-21
10. Thompson N, Lyons J. Recent progress in targeting the Raf/MEK/ERK pathway with inhibitors in cancer drug discovery. Curr Opin Pharmacol 2005;5:350-6
11. Adjei AA. The role of mitogen-Activated ERK kinase inhibitors in lung cancer therapy. Clin Lung Cancer 2005;7:221-3
12. Wallace EM, Lyssikatos JP, Yeh T, et al. Progress towards therapeutic small molecule MEK inhibitors for use in cancer therapy. Curr Top Med Chem 2005;5:215-29
13. Morgillo F, Cascone T, D'Aiuto E, et al. Antitumour efficacy of MEK inhibitors in human lung cancer cells and their derivatives with acquired resistance to different tyrosine kinase inhibitors. Br J Cancer 2011;105:382-92
14. Allen LF, Sebolt-Leopold J, Meyer MB. CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK). Semin Oncol 2003;30(Suppl 16):105-16
15. McDaid HM, Lopez-Barcons L, Grossman A, et al. Enhancement of the therapeutic efficacy of taxol by the mitogen-Activated protein kinase kinase inhibitor CI-1040 in nude mice bearing human heterotransplants. Cancer Res 2005;65:2854-60
16. Lorusso PM, Adjei AA, Varterasian M, et al. Phase I and pharmacodynamic study of the oral MEK inhibitor CI-1040 in patients with advanced malignancies. J Clin Oncol 2005;23:5281-93
17. Rinehart J, Adjei AA, Lorusso PM, et al. Multicenter phase II study of the oral MEK inhibitor, CI-1040, in patients with advanced non-small-cell lung, breast, colon, and pancreatic cancer. J Clin Oncol 2004;22:4456-62
18. Trejo CL, Juan J, Vicent S, et al. MEK1/2 inhibition elicits regression of autochthonous lung tumors induced by KRASG12D or BRAFV600E. Cancer Res 2012;72:3048-59
19. Brown AP, Carlson TC, Loi CM, Graziano MJ. Pharmacodynamic and toxicokinetic evaluation of the novel MEK inhibitor, PD0325901, in the rat following oral and intravenous administration. Cancer Chemother Pharmacol 2007;59:671-9
20. LoRusso PM, Krishnamurthi SS, Rinehart JJ, et al. Phase I pharmacokinetic and pharmacodynamic study of the oral MAPK/ERK kinase inhibitor PD-0325901 in patients with advanced cancers. Clin Cancer Res 2010;16:1924-37
21. Haura EB, Ricart AD, Larson TG, et al. A phase II study of PD-0325901, an oral MEK inhibitor, in previously treated patients with advanced non-small cell lung cancer. Clin Cancer Res 2010;16:2450-7
22. Halilovic E, She QB, Ye Q, et al. PIK3CA mutation uncouples tumor growth and cyclin D1 regulation from MEK/ERK and mutant KRAS signaling. Cancer Res 2010;70:6804-14
23. Legrier ME, Yang CP, Yan HG, et al. Targeting protein translation in human non small cell lung cancer via combined MEK and mammalian target of rapamycin suppression. Cancer Res 2007;67:11300-8
24. Simmons BH, Lee JH, Lalwani K, et al. Combination of a MEK inhibitor at sub-MTD with a PI3K/mTOR inhibitor significantly suppresses growth of lung adenocarcinoma tumors in Kras (G12D-LSL) mice. Cancer Chemother Pharmacol 2012;70:213-20
25. Troiani T, Vecchione L, Martinelli E, et al. Intrinsic resistance to selumetinib, a selective inhibitor of MEK1/2, by cAMP-dependent protein kinase A activation in human lung and colorectal cancer cells. Br J Cancer 2012;106(10):1648-59
26. Holt SV, Logie A, Davies BR, et al. Enhanced apoptosis and tumor growth suppression elicited by combination of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055). Cancer Res 2012;72:1804-13
27. Chung EJ, Brown AP, Asano H, et al. In vitro and in vivo radiosensitization with AZD6244 (ARRY-142886), an inhibitor of mitogen-Activated protein kinase/extracellular signal-regulated kinase 1/2 kinase. Clin Cancer Res 2009;15:3050-7
28. Adjei AA, Cohen RB, Franklin W, et al. Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-Activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers. J Clin Oncol 2008;26:2139-46
29. Hainsworth JD, Cebotaru CL, Kanarev V, et al. A phase II, open-label, randomized study to assess the efficacy and safety of AZD6244 (ARRY-142886) versus pemetrexed in patients with non-small cell lung cancer who have failed one or two prior chemotherapeutic regimens. J Thorac Oncol 2010;5:1630-6
30. Jänne PA, Shaw AT, Pereira JR, et al. Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study. Lancet Oncol 2013;14:38-47
31. Iverson C, Larson G, Lai C, et al. RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer. Cancer Res 2009;69:6839-47
32. Liu N, Puehler F, Haegebarth A, et al. Combination of PI3K inhibitor BAY 80-6946 with allosteric MEK inhibitor BAY 86-9766 (RDEA119) and with erlotinib for the treatment of non-small cell lung cancer [abstract 140]. 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics; Berlin; 2010
33. Weekes CD, Von Hoff DD, Adjei AA, et al. Multicenter phase I trial of the mitogen-Activated protein kinase 1/2 inhibitor BAY 86-9766 in patients with advanced cancer. Clin Cancer Res 2013;19:1232-43
34. Martinelli E, Troiani T, D'Aiuto E, et al. Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells. Int J Cancer 2013;133:2089-101
35. Infante JR, Gandi L, Shapiro G, et al. Combination of the MEK inhibitor, pimasertib (MSC1936369B), and the PI3K/mTOR inhibitor, SAR245409, in patients with advanced solid tumors: results of a phase Ib dose-escalation trial. Cancer Res 2013;73(Suppl 1):abstract LB-147
36. Isshiki Y, Kohchi Y, Iikura H, et al. Design and synthesis of novel allosteric MEK inhibitor CH4987655 as an orally available anticancer agent. Bioorg Med Chem Lett 2011;21:1795-801
37. Lee L, Niu H, Rueger R, et al. The safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of CH4987655 in healthy volunteers: target suppression using a biomarker. Clin Cancer Res 2009;15:7368-74
38. Leijen S, Middleton MR, Tresca P, et al. Phase I dose-escalation study of the safety, pharmacokinetics, and pharmacodynamics of the MEK inhibitor RO4987655 (CH4987655) in patients with advanced solid tumors. Clin Cancer Res 2012;18:4794-805
39. Gilmartin AG, Bleam MR, Groy A, et al. GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition. Clin Cancer Res 2011;17:989-1000
40. Infante JR, Fecher LA, Falchook GS, et al. Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial. Lancet Oncol 2012;13:773-81
41. Infante JR, Papadopoulos KP, Bendell JC, et al. A phase 1b study of trametinib, an oral Mitogen-Activated protein kinase kinase (MEK) inhibitor, in combination with gemcitabine in advanced solid tumours. Eur J Cancer 2013;49(9):2077-85
42. Becerra C, Infante JR, Garbo LE, et al. A five-Arm, open-label, phase I/lb study to assess safety and tolerability of the oral MEK1/MEK2 inhibitor trametinib (GSK1120212) in combination with chemotherapy or erlotinib in patients with advanced solid tumors. J Clin Oncol 2012;30(Suppl): abstract 3023
43. Gandara DR, Hiret S, Blumenschein GR, et al. Oral MEK1/MEK2 inhibitor trametinib (GSK1120212) in combination with docetaxel in KRAS-mutant and wild-type (WT) advanced non-small cell lung cancer (NSCLC): a phase I/Ib trial. J Clin Oncol 2013;31(Suppl): abstract 8028
44. Mazieres J, Gandara DR, Leighl N, et al. Oral MEK1/MEK2 inhibitor trametinib (GSK1120212) in combination with pemetrexed in a phase 1/1B trial involving KRAS-mutant and wild-type (WT) advanced non-small cell lung cancer (NSCLC): efficacy and biomarker results [abstract MO18.10]. Presentation time: Tuesday, 29 October 2013; Abstract MO18.10 15th World Conference on Lung Cancer; 27-30 October 2013; Sydney, Australia
45. Blumenschein GR, Smit EF, Planchard D, et al. MEK114653: A randomized, multicenter, phase II study to assess efficacy and safety of trametinib (T) compared with docetaxel (D) in KRAS-mutant advanced non-small cell lung cancer (NSCLC). J Clin Oncol 2013;31(Suppl):abstract 8029
46. Adjei AA, LoRusso PM, Ribas A, et al. Phase I, dose-escalation study of the investigational drug TAK-733, an oral MEK inhibitor, in patients (pts) with advanced solid tumors. JCO 2013(Suppl):abstract 2528
47. Lee PA, Wallace E, Marlow A, et al. Preclinical Development of ARRY-162, a potent and selective MEK 1/2 inhibitor. Cancer Res 2010;70(1):abstract 2515
48. Bendell JC, Papadopoulos K, Jones SF, et al. A phase I dose-escalation study of MEK inhibitor MEK162 (ARRY-438162) in patients with advanced solid tumors. Mol Cancer Ther 2011;10(Suppl 1):abstract B243
49. Shimokata T, Watanabe K, Shibata T, et al. Results of a phase 1 study of MEK162, an oral MEK inhibitor, in Japanese patients with advanced solid tumors [abstract 3746]. 7th ECCO-38th ESMO-32nd ESTRO European Cancer Congress; 27 September-1 October 2013; Amsterdam, The Netherlands
50. ASCO MEETING ABSTRACTS. A phase I, first-in-human single ascending dose study of the MEK inhibitor WX-554 given to healthy male subjects [abstract e13666]. ASCO ANNUAL MEETING; Chicago; 2010
51. Choo EF, Belvin M, Boggs J, et al. Preclinical disposition of GDC-0973 and prospective and retrospective analysis of human dose and efficacy predictions. DMD 2012;40:919-27
52. Rosen LS, Galatin P, Fehling JM, et al. A phase 1 dose-escalation study of XL518, a potent MEK inhibitor administered orally daily to subjects with solid tumors. J Clin Oncol [abstract] 2008;26:14585
53. Balsara BR, Pei J, Mitsuuchi Y, et al. Frequent activation of AKT in non-small cell lung carcinomas and preneoplastic bronchial lesions. Carcinogenesis 2004;25:2053-9
54. Tsurutani J, Fukuoka J, Tsurutani H, et al. Evaluation of two phosphorylation sites improves the prognostic significance of Akt activation in non-small-cell lung cancer tumors. J Clin Oncol 2006;24:306-14
55. Forgacs E, Biesterveld EJ, Sekido Y, et al. Mutation analysis of the PTEN/MMAC1 gene in lung cancer. Oncogene 1998;17:1557-65
56. Malanga D, Scrima M, De Marco C, et al. Activating E17K mutation in the gene encoding the protein kinase AKT1 in a subset of squamous cell carcinoma of the lung. Cell Cycle 2008;7:665-9
57. Castellano E, Downward J. Role of RAS in the regulation of PI3-kinase. Curr Top Microbiol Immunol 2010;346:143-69
58. Hirai H, Sootome H, Nakatsuru Y, et al. MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Ther 2010;9:1956-67
59. Mack PC, Farneth N, Mahaffey C, et al. Impact of AKT inhibitor MK-2206 on erlotinib resistance in non-small cell lung cancer (NSCLC). J Ciln Oncol 2011;29(Suppl):7573
60. Lida M, Brand TM, Campbell DA, et al. Targeting AKT with the allosteric AKT inhibitor MK-2206 in non-small cell lung cancer cells with acquired resistance to cetuximab. Cancer Biol Ther 2013;14(6):481-91
61. Yap TA, Patnaik A, Fearen I, et al. First-in-class phase I trial of a selective Akt inhibitor, MK2206 (MK), evaluating alternate day (QOD) and once weekly (QW) doses in advanced cancer patients (pts) with evidence of target modulation and antitumor activity. J Clin Oncol 2010;28(Suppl):3009
62. Tolcher AW, Baird RD, Patnaik A, et al. A phase I dose-escalation study of oral MK-2206 (allosteric AKT inhibitor) with oral selumetinib (AZD6244; MEK inhibitor) in patients with advanced or metastatic solid tumors. J Clin Oncol 2011;29(Suppl):abstract 3004
63. de Bono J, Baird R, Patnaik A, et al. A phase I dose escalation study of oral MK-2206 (allosteric AKT Inhibitor) with oral selumetinib (AZD6244; ARRY-142866) (MEK Inhibitor) in patients with advanced or metastatic solid tumours. 7th NCRI Conference; Liverpool; 2014
64. Molife LR, Yan L, Vitfell-Rasmussen J, et al. Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors. J Hematol Oncol 2014;7(1):1
65. Mazzitello C, Esposito S, De Francesco AE, et al. Pharmacovigilance in Italy: an overview. J Pharmacol Pharmacother 2013;4(Suppl):S20-8
66. Parretta E, Ianniello B, Ferrazin F, et al. Italian post-marketing surveillance for adverse event reports after MF59-Adjuvanted H1N1v vaccination. Vaccine 2011;29(20):3708-13