Mer590, a novel monoclonal antibody targeting MER receptor tyrosine kinase, decreases colony formation and increases chemosensitivity in non-small cell lung cancer

Oncotarget

Volumn 5, Issue 21, 2014, Pages 10434-10445

  Cummings, Christopher T ^a,b   Linger, Rachel M A ^a,b,e   Cohen, Rebecca A ^a,b   Sather, Susan ^a,b   Kirkpatrick, Gregory D ^a,b   Davies, Kurtis D ^a,b   DeRyckere, Deborah ^a,b   Shelton Earp, H ^c,d   Graham, Douglas K ^a,b  

^a Section of Hematology   (United States)

^b UNIVERSITY OF COLORADO   (United States)

^c UNIVERSITY OF NORTH CAROLINA   (United States)

^d UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^e Rocky Vista University   (United States)

Author keywords

Chemosensitivity; MER; Monoclonal antibody; NSCLC; Targeted therapy

Indexed keywords

CARBOPLATIN; MER 590; MITOGEN ACTIVATED PROTEIN KINASE 1; MONOCLONAL ANTIBODY; PROTEIN KINASE B; PROTEIN MER; PROTEIN TYROSINE KINASE; SHORT HAIRPIN RNA; STAT6 PROTEIN; UNCLASSIFIED DRUG; MERTK PROTEIN, HUMAN; MITOGEN ACTIVATED PROTEIN KINASE 3; ONCOPROTEIN; PROTEIN KINASE INHIBITOR; SMALL INTERFERING RNA;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER INHIBITION; CHEMOSENSITIVITY; COLONY FORMATION; DRUG PROTEIN BINDING; DRUG TARGETING; HUMAN; HUMAN CELL; NON SMALL CELL LUNG CANCER; PROTEIN DEGRADATION; PROTEIN SYNTHESIS INHIBITION; RECEPTOR DOWN REGULATION; SIGNAL TRANSDUCTION; CARCINOMA, NON-SMALL-CELL LUNG; DOWN REGULATION; DRUG EFFECTS; DRUG POTENTIATION; DRUG RESISTANCE; DRUG SCREENING; GENE EXPRESSION REGULATION; GENETICS; IMMUNOLOGY; LUNG NEOPLASMS; METABOLISM; MOLECULARLY TARGETED THERAPY; TUMOR CELL LINE;

ANTIBODIES, MONOCLONAL; APOPTOSIS; CARBOPLATIN; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; DOWN-REGULATION; DRUG RESISTANCE; DRUG SYNERGISM; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; LUNG NEOPLASMS; MITOGEN-ACTIVATED PROTEIN KINASE 1; MITOGEN-ACTIVATED PROTEIN KINASE 3; MOLECULAR TARGETED THERAPY; ONCOGENE PROTEIN V-AKT; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS; RECEPTOR PROTEIN-TYROSINE KINASES; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; STAT6 TRANSCRIPTION FACTOR; TUMOR STEM CELL ASSAY;

EID: 84916888486     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.2142     Document Type: Article

References (35)

1. Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH, Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002; 346: 92-8.
2. Kelly K, Crowley J, Bunn PA Jr., Presant CA, Grevstad PK, Moinpour CM, Ramsey SD, Wozniak AJ, Weiss GR, Moore DF, Israel VK, Livingston RB, Gandara DR. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol. 2001; 19: 3210-8.
3. Carney DN. Lung Cancer-Time to Move on from Chemotherapy. N Engl J Med. 2002; 346: 126-8.
4. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010; 362: 2380-8.
5. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005; 353: 123-32.
6. Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013; 31: 3327-34.
7. Shaw AT, Kim DW, Nakagawa K, Seto T, Crino L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013; 368: 2385-94.
8. Minuti G, D'Incecco A, Cappuzzo F. Targeted therapy for NSCLC with driver mutations. Expert Opin Biol Ther. 2013; 13: 1402-12.
9. Slikowski MX, Mellman I. Antibody therapeutics in cancer. Science. 2013; 341: 1192-8.
10. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006; 355: 2542-50.
11. Demarest SJ, Gardner J, Vendel MC, Ailor E, Szak S, Huang F, Doern A, Tan X, Yang W, Grueneberg DA, Richards EJ, Endege WO, Harlow E, Koopman LA. Evaluation of Tyro3 expression, Gas6-mediated Akt phosphorylation, and the impact of anti-Tyro3 antibodies in melanoma cell lines. Biochemistry. 2013; 52: 3102-18.
12. Ye X, Li Y, Stawicki S, Couto S, Eastham-Anderson J, Kallop D, Weimer R, Wu Y, Pei L. An anti-Axl monoclonal antibody attenuates xenograft tumor growth and enhances the effect of multiple anticancer therapies. Oncogene. 2010; 29: 5254-64.
13. Linger RM, Cohen RA, Cummings CT, Sather S, Migdall-Wilson J, Middleton DH, Lu X, Baron AE, Franklin WA, Merrick DT, Jedlicka P, DeRyckere D, Heasley LE, Graham DK. Mer or Axl receptor tyrosine kinase inhibition promotes apoptosis, blocks growth and enhances chemosensitivity of human non-small cell lung cancer. Oncogene. 2013; 32: 3420-31.
14. Linger RM, Lee-Sherick AB, DeRyckere D, Cohen RA, Jacobsen KM, McGranahan A, Brandao LN, Winges A, Sawczyn KK, Liang X, Keating AK, Tan AC, Earp HS, Graham DK. Mer receptor tyrosine kinase is a therapeutic target in pre-B-cell acute lymphoblastic leukemia. Blood. 2013; 122: 1599-609.
15. Keating AK, Salzberg DB, Sather S, Liang X, NickoloffS, Anwar A, Deryckere D, Hill K, Joung D, Sawczyn KK, Park J, Curran-Everett D, McGavran L, Meltesen L, Gore L, Johnson GL, Graham DK. Lymphoblastic leukemia/lymphoma in mice overexpressing the Mer (MerTK) receptor tyrosine kinase. Oncogene. 2006; 25: 6092-100.
16. Brandao LN, Winges A, Christoph S, Sather S, Migdall-Wilson J, Schlegel J, McGranahan A, Gao D, Liang X, Deryckere D, Graham DK. Inhibition of MerTK increases chemosensitivity and decreases oncogenic potential in T-cell acute lymphoblastic leukemia. Blood Cancer J. 2013; 3: e101.
17. Graham DK, Salzberg DB, Kurtzberg J, Sather S, Matsushima GK, Keating AK, Liang X, Lovell MA, Williams SA, Dawson TL, Schell MJ, Anwar AA, Snodgrass HR, Earp HS. Ectopic expression of the proto-oncogene Mer in pediatric T-cell acute lymphoblastic leukemia. Clin Cancer Res. 2006; 12: 2662-9.
18. Lee-Sherick AB, Eisenman KM, Sather S, McGranahan A, Armistead PM, McGary CS, Hunsucker SA, Schlegel J, Martinson H, Cannon C, Keating AK, Earp HS, Liang X, DeRyckere D, Graham DK. Aberrant Mer receptor tyrosine kinase expression contributes to leukemogenesis in acute myeloid leukemia. Oncogene. 2013; 32: 5359-68.
19. Schlegel J, Sambade MJ, Sather S, Moschos SJ, Tan AC, Winges A, DeRyckere D, Carson CC, Trembath DG, Tentler JJ, Eckhardt SG, Kuan PF, Hamilton RL, Duncan LM, Miller CR, Mikolaishvili-Feinberg N. MERTK receptor tyrosine kinase is a therapeutic target in melanoma. J Clin Invest. 2013; 123: 2257-67.
20. Keating AK, Kim GK, Jones AE, Donson AM, Ware K, Mulcahy JM, Salzberg DB, Foreman NK, Liang X, Thorburn A, Graham DK. Inhibition of Mer and Axl receptor tyrosine kinases in astrocytoma cells leads to increased apoptosis and improved chemosensitivity. Mol Cancer Ther. 2010; 9: 1298-307.
21. Wu YM, Robinson DR, Kung HJ. Signal pathways in up-regulation of chemokines by tyrosine kinase MER/NYK in prostate cancer cells. Cancer Res. 2004; 64: 7311-20.
22. Cummings CT, Deryckere D, Earp HS, Graham DK. Molecular pathways: MERTK signaling in cancer. Clin Cancer Res. 2013; 19: 5275-80.
23. Liu J, Yang C, Simpson C, Deryckere D, Van Deusen A, Miley MJ, Kireev D, Norris-Drouin J, Sather S, Hunter D, Korboukh VK, Patel HS, Janzen WP, Machius M, Johnson GL, Earp HS, et al. Discovery of Novel Small Molecule Mer Kinase Inhibitors for the Treatment of Pediatric Acute Lymphoblastic Leukemia. ACS Med Chem Lett. 2012; 3: 129-34.
24. Liu J, Zhang W, Stashko MA, Deryckere D, Cummings CT, Hunter D, Yang C, Jayakody CN, Cheng N, Simpson C, Norris-Drouin J, Sather S, Kireev D, Janzen WP, Earp HS, Graham DK, et al. UNC1062, a new and potent Mer inhibitor. Eur J Med Chem. 2013; 65: 83-93.
25. Christoph S, Deryckere D, Schlegel J, Frazer JK, Batchelor LA, Trakhimets AY, Sather S, Hunter DM, Cummings CT, Liu J, Yang C, Kireev D, Simpson C, Norris-Drouin J, Hull-Ryder EA, Janzen WP, et al. UNC569, a novel small-molecule mer inhibitor with efficacy against acute lymphoblastic leukemia in vitro and in vivo. Mol Cancer Ther. 2013; 12: 2367-77.
26. Zhang W, Zhang D, Stashko MA, DeRyckere D, Hunter D, Kireev D, Miley MJ, Cummings C, Lee M, Norris-Drouin J, Stewart WM, Sather S, Zhou Y, Kirkpatrick G, Machius M, Janzen WP, et al. Pseudo-cyclization through intramolecular hydrogen bond enables discovery of pyridine substituted pyrimidines as new Mer kinase inhibitors. J Med Chem. 2013; 56: 9683-92.
27. Rogers AE, Le JP, Sather S, Pernu BM, Graham DK, Pierce AM, Keating AK. Mer receptor tyrosine kinase inhibition impedes glioblastoma multiforme migration and alters cellular morphology. Oncogene. 2012; 31: 4171-81.
28. Petrelli A, Circosta P, Granziero L, Mazzone M, Pisacane A, Fenoglio S, Comoglio PM, Giordano S. Ab-induced ectodomain shedding mediates hepatocyte growth factor receptor down-regulation and hampers biological activity. Proc Natl Acad Sci U S A. 2006; 103: 5090-5.
29. Lee JM, Kim B, Lee SB, Jeong Y, Oh YM, Song YJ, Jung S, Choi J, Lee S, Cheong KH, Kim DU, Park HW, Han YK, Kim GW, Choi H, Song PH, et al. Cbl-independent degradation of Met: ways to avoid agonism of bivalent Met-targeting antibody. Oncogene. 2014; 33: 34-43.
30. Sather S, Kenyon KD, Lefkowitz JB, Liang X, Varnum BC, Henson PM, Graham DK. A soluble form of the Mer receptor tyrosine kinase inhibits macrophage clearance of apoptotic cells and platelet aggregation. Blood. 2007; 109: 1026-33.
31. Huang LJ, Chen SX, Luo WJ, Jiang HH, Zhang PF, Yi H. Proteomic analysis of secreted proteins of non-small cell lung cancer. Ai Zheng. 2006; 25: 1361-7.
32. Duex JE, Mullins MR, Sorkin A. Recruitment of Uev1B to Hrs-containing endosomes and its effect on endosomal trafficking. Exp Cell Res. 2010; 316: 2136-51.
33. Brenner T, Shrina D, Natale J, Wirth SM. Treatment protocols for non-small cell lung cancer. UpToDate. Jul 13 2012. www.uptodate.com. Accessed Jan 24, 2014.
34. Berenbaum MC. What is synergy? Pharmacol Rev. 1989; 41: 93-141.
35. Tebbutt N, Pedersen MW, Johns TG. Targeting the ERBB family in cancer: couples therapy. Nat Rev Cancer. 2013; 13: 663-73.