Niche-Based screening in multiple myeloma identifies a kinesin-5 inhibitor with improved selectivity over hematopoietic progenitors

Cell Reports

Volumn 10, Issue 5, 2015, Pages 755-770

  Chattopadhyay, Shrikanta ^a,b   Stewart, Alison L ^a   Mukherjee, Siddhartha ^c   Huang, Cherrie ^a,b   Hartwell, Kimberly A ^a   Miller, Peter G ^d,m   Subramanian, Radhika ^e   Carmody, Leigh C ^a   Yusuf, Rushdia Z ^b   Sykes, David B ^b   Paulk, Joshiawa ^a,g   Vetere, Amedeo ^a   Vallet, Sonia ^b   Santo, Loredana ^b   Cirstea, Diana D ^f   Hideshima, Teru ^f   Dančík, Vlado ^a   Majireck, Max M ^a,g   Hussain, Mahmud M ^a,g,n   Singh, Shambhavi ^a,g   Quiroz, Ryan ^a,h   Iaconelli, Jonathan ^a,i   Karmacharya, Rakesh ^a,i,j   Tolliday, Nicola J ^a   Clemons, Paul A ^a   Moore, MalcolmA S ^k   Stern, Andrew M ^a,l   Shamji, Alykhan F ^a   Ebert, Benjamin L ^f,m   Golub, Todd R ^a,f,n   Raje, Noopur S ^b   Scadden, David T ^b,d,g   Schreiber, Stuart L ^a,g,n   more..

^a BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

^c Columbia University School of Medicine ^*  (United States)

^d HARVARD MEDICAL SCHOOL   (United States)

^e ROCKEFELLER UNIVERSITY   (United States)

^f DANA FARBER CANCER INSTITUTE   (United States)

^g HARVARD UNIVERSITY   (United States)

^h UNIVERSITY OF CALIFORNIA   (United States)

ⁱ MASSACHUSETTS GENERAL HOSPITAL   (United States)

^j MCLEAN HOSPITAL   (United States)

^k MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^l UNIVERSITY OF PITTSBURGH   (United States)

^m BRIGHAM AND WOMEN S HOSPITAL   (United States)

ⁿ HOWARD HUGHES MEDICAL INSTITUTE   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BRD 9876; EG5 PROTEIN; KINESIN 5; ONCOPROTEIN; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; BONE MARROW STROMA CELL; CANCER RESISTANCE; CANCER SCREENING; COCULTURE; CONTROLLED STUDY; DRUG EFFICACY; DRUG SCREENING; DRUG SELECTIVITY; HEMATOPOIETIC STEM CELL; HUMAN; HUMAN CELL; MICROTUBULE; MULTIPLE MYELOMA; MULTIPLE MYELOMA CELL LINE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN PHOSPHORYLATION; PROTEIN TARGETING;

EID: 84923351242     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2015.01.017     Document Type: Article

References (51)

1. Adams J., Behnke M., Chen S., Cruickshank A.A., Dick L.R., Grenier L., Klunder J.M., Ma Y.T., Plamondon L., Stein R.L. Potent and selective inhibitors of the proteasome: dipeptidyl boronic acids. Bioorg. Med. Chem. Lett. 1998, 8:333-338.
2. Alberts D.S., Salmon S.E. Adriamycin (NSC-123127) in the treatment of alkylator-resistant multiple myeloma: a pilot study. Cancer Chemother. Rep. 1975, 59:345-350.
3. Bagley R.G., Roth S., Kurtzberg L.S., Rouleau C., Yao M., Crawford J., Krumbholz R., Lovett D., Schmid S., Teicher B.A. Bone marrow CFU-GM and human tumor xenograft efficacy of three antitumor nucleoside analogs. Int. J. Oncol. 2009, 34:1329-1340.
4. Bartlett J.B., Dredge K., Dalgleish A.G. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat. Rev. Cancer 2004, 4:314-322.
5. Blangy A., Lane H.A., d'Hérin P., Harper M., Kress M., Nigg E.A. Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation invivo. Cell 1995, 83:1159-1169.
6. Burris H.A., Jones S.F., Williams D.D., Kathman S.J., Hodge J.P., Pandite L., Ho P.T., Boerner S.A., Lorusso P. A phase I study of ispinesib, a kinesin spindle protein inhibitor, administered weekly for three consecutive weeks of a 28-day cycle in patients with solid tumors. Invest. New Drugs 2011, 29:467-472.
7. Chatterjee M., Hönemann D., Lentzsch S., Bommert K., Sers C., Herrmann P., Mathas S., Dörken B., Bargou R.C. In the presence of bone marrow stromal cells human multiple myeloma cells become independent of the IL-6/gp130/STAT3 pathway. Blood 2002, 100:3311-3318.
8. Dalton W., Anderson K.C. Synopsis of a roundtable on validating novel therapeutics for multiple myeloma. Clin. Cancer Res. 2006, 12:6603-6610.
9. Decaux O., Lodé L., Magrangeas F., Charbonnel C., Gouraud W., Jézéquel P., Attal M., Harousseau J.L., Moreau P., Bataille R., et al. Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the Intergroupe Francophone du Myélome. J.Clin. Oncol. 2008, 26:4798-4805. Intergroupe Francophone du Myélome.
10. Dimopoulos M.A., Arbuck S., Huber M., Weber D., Luckett R., Delasalle K., Alexanian R. Primary therapy of multiple myeloma with paclitaxel (taxol). Ann. Oncol. 1994, 5:757-759.
11. El-Nassan H.B. Advances in the discovery of kinesin spindle protein (Eg5) inhibitors as antitumor agents. Eur. J. Med. Chem. 2013, 62:614-631.
12. Erickson-Miller C.L., May R.D., Tomaszewski J., Osborn B., Murphy M.J., Page J.G., Parchment R.E. Differential toxicity of camptothecin, topotecan and 9-aminocamptothecin to human, canine, and murine myeloid progenitors (CFU-GM) invitro. Cancer Chemother. Pharmacol. 1997, 39:467-472.
13. Fenteany G., Standaert R.F., Lane W.S., Choi S., Corey E.J., Schreiber S.L. Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. Science 1995, 268:726-731.
14. Ferlay, J., Soerjomataram, I., Ervik, M., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Parkin, D.M., Forman, D., and Bray, F. (2013). GLOBOCAN 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012. http://globocan.iarc.fr.
15. Feugier P., Li N., Jo D.Y., Shieh J.H., MacKenzie K.L., Lesesve J.F., Latger-Cannard V., Bensoussan D., Crystal R.G., Rafii S., et al. Osteopetrotic mouse stroma with thrombopoietin, c-kit ligand, and flk-2 ligand supports long-term mobilized CD34+ hematopoiesis invitro. Stem Cells Dev. 2005, 14:505-516.
16. Hideshima T., Chauhan D., Shima Y., Raje N., Davies F.E., Tai Y.T., Treon S.P., Lin B., Schlossman R.L., Richardson P., et al. Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood 2000, 96:2943-2950.
17. Hideshima T., Richardson P., Chauhan D., Palombella V.J., Elliott P.J., Adams J., Anderson K.C. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res. 2001, 61:3071-3076.
18. Hideshima T., Mitsiades C., Tonon G., Richardson P.G., Anderson K.C. Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat. Rev. Cancer 2007, 7:585-598.
19. Jones R., Vuky J., Elliott T., Mead G., Arranz J.A., Chester J., Chowdhury S., Dudek A.Z., Müller-Mattheis V., Grimm M.O., et al. Phase II study to assess the efficacy, safety and tolerability of the mitotic spindle kinesin inhibitor AZD4877 in patients with recurrent advanced urothelial cancer. Invest. New Drugs 2013, 31:1001-1007.
20. Kim E.D., Buckley R., Learman S., Richard J., Parke C., Worthylake D.K., Wojcik E.J., Walker R.A., Kim S. Allosteric drug discrimination is coupled to mechanochemical changes in the kinesin-5 motor core. J.Biol. Chem. 2010, 285:18650-18661.
21. Krajewska M., Heijink A.M., Bisselink Y.J., Seinstra R.I., Silljé H.H., de Vries E.G., van Vugt M.A. Forced activation of Cdk1 via wee1 inhibition impairs homologous recombination. Oncogene 2013, 32:3001-3008.
22. Kurtzberg L.S., Roth S.D., Bagley R.G., Rouleau C., Yao M., Crawford J.L., Krumbholz R.D., Schmid S.M., Teicher B.A. Bone marrow CFU-GM and human tumor xenograft efficacy of three tubulin binding agents. Cancer Chemother. Pharmacol. 2009, 64:1029-1038.
23. Lad L., Luo L., Carson J.D., Wood K.W., Hartman J.J., Copeland R.A., Sakowicz R. Mechanism of inhibition of human KSP by ispinesib. Biochemistry 2008, 47:3576-3585.
24. Lamb J., Crawford E.D., Peck D., Modell J.W., Blat I.C., Wrobel M.J., Lerner J., Brunet J.P., Subramanian A., Ross K.N., et al. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science 2006, 313:1929-1935.
25. Lohr J.G., Stojanov P., Carter S.L., Cruz-Gordillo P., Lawrence M.S., Auclair D., Sougnez C., Knoechel B., Gould J., Saksena G., et al. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell 2014, 25:91-101. Multiple Myeloma Research Consortium.
26. Luo L., Carson J.D., Dhanak D., Jackson J.R., Huang P.S., Lee Y., Sakowicz R., Copeland R.A. Mechanism of inhibition of human KSP by monastrol: insights from kinetic analysis and the effect of ionic strength on KSP inhibition. Biochemistry 2004, 43:15258-15266.
27. Luo L., Parrish C.A., Nevins N., McNulty D.E., Chaudhari A.M., Carson J.D., Sudakin V., Shaw A.N., Lehr R., Zhao H., et al. ATP-competitive inhibitors of the mitotic kinesin KSP that function via an allosteric mechanism. Nat. Chem. Biol. 2007, 3:722-726.
28. Man C., Rosa J., Yip Y.L., Cheung A.L., Kwong Y.L., Doxsey S.J., Tsao S.W. Id1 overexpression induces tetraploidization and multiple abnormal mitotic phenotypes by modulating aurora A. Mol. Biol. Cell 2008, 19:2389-2401.
29. Matsuo Y., Drexler H.G., Nishizaki C., Harashima A., Fukuda S., Kozuka T., Sezaki T., Orita K. Human bone marrow stroma-dependent cell line MOLP-5 derived from a patient in leukaemic phase of multiple myeloma. Br. J. Haematol. 2000, 109:54-63.
30. Mayer T.U., Kapoor T.M., Haggarty S.J., King R.W., Schreiber S.L., Mitchison T.J. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science 1999, 286:971-974.
31. McMillin D.W., Delmore J., Weisberg E., Negri J.M., Geer D.C., Klippel S., Mitsiades N., Schlossman R.L., Munshi N.C., Kung A.L., et al. Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity. Nat. Med. 2010, 16:483-489.
32. Meads M.B., Hazlehurst L.A., Dalton W.S. The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance. Clin. Cancer Res. 2008, 14:2519-2526.
33. Musacchio A., Salmon E.D. The spindle-assembly checkpoint in space and time. Nat. Rev. Mol. Cell Biol. 2007, 8:379-393.
34. Nielsen T.E., Schreiber S.L. Towards the optimal screening collection: a synthesis strategy. Angew. Chem. Int. Ed. Engl. 2008, 47:48-56.
35. Olaharski A.J., Uppal H., Cooper M., Platz S., Zabka T.S., Kolaja K.L. Invitro to invivo concordance of a high throughput assay of bone marrow toxicity across a diverse set of drug candidates. Toxicol. Lett. 2009, 188:98-103.
36. Owens B. Kinesin inhibitor marches toward first-in-class pivotal trial. Nat. Med. 2013, 19:1550.
37. Parchment R.E., Gordon M., Grieshaber C.K., Sessa C., Volpe D., Ghielmini M. Predicting hematological toxicity (myelosuppression) of cytotoxic drug therapy from invitro tests. Ann. Oncol. 1998, 9:357-364.
38. Pessina A., Albella B., Bayo M., Bueren J., Brantom P., Casati S., Croera C., Gagliardi G., Foti P., Parchment R., et al. Application of the CFU-GM assay to predict acute drug-induced neutropenia: an international blind trial to validate a prediction model for the maximum tolerated dose (MTD) of myelosuppressive xenobiotics. Toxicol. Sci. 2003, 75:355-367.
39. Purcell J.W., Davis J., Reddy M., Martin S., Samayoa K., Vo H., Thomsen K., Bean P., Kuo W.L., Ziyad S., et al. Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast cancer. Clin. Cancer Res. 2010, 16:566-576.
40. Rath A., Glibowicka M., Nadeau V.G., Chen G., Deber C.M. Detergent binding explains anomalous SDS-PAGE migration of membrane proteins. Proc. Natl. Acad. Sci. USA 2009, 106:1760-1765.
41. Richardson P.G., Sonneveld P., Schuster M.W., Irwin D., Stadtmauer E.A., Facon T., Harousseau J.L., Ben-Yehuda D., Lonial S., Goldschmidt H., et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N.Engl. J. Med. 2005, 352:2487-2498. Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators.
42. Shah J.J., Zonder J., Cohen A., Orlowski R.Z., Alexanian R., Thomas S.K., Weber D., Kaufman J.L., Harvey R.D., Walker D., et al. ARRY-520 shows durable responses in patients with relapsed/refractory multiple myeloma in a phase 1 dose-escalation study. ASH Annual Meeting Abstracts 2011, 118:1860.
43. Swinney D.C., Anthony J. How were new medicines discovered?. Nat. Rev. Drug Discov. 2011, 10:507-519.
44. Talapatra S.K., Schüttelkopf A.W., Kozielski F. The structure of the ternary Eg5-ADP-ispinesib complex. Acta Crystallogr. D Biol. Crystallogr. 2012, 68:1311-1319.
45. Tillement V., Remy M.H., Raynaud-Messina B., Mazzolini L., Haren L., Merdes A. Spindle assembly defects leading to the formation of a monopolar mitotic apparatus. Biol. Cell 2009, 101:1-11.
46. Ulaganathan V., Talapatra S.K., Rath O., Pannifer A., Hackney D.D., Kozielski F. Structural insights into a unique inhibitor binding pocket in kinesin spindle protein. J.Am. Chem. Soc. 2013, 135:2263-2272.
47. Vassilev L.T., Tovar C., Chen S., Knezevic D., Zhao X., Sun H., Heimbrook D.C., Chen L. Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1. Proc. Natl. Acad. Sci. USA 2006, 103:10660-10665.
48. Woessner R., Tunquist B., Lemieux C., Chlipala E., Jackinsky S., Dewolf W., Voegtli W., Cox A., Rana S., Lee P., Walker D. ARRY-520, a novel KSP inhibitor with potent activity in hematological and taxane-resistant tumor models. Anticancer Res. 2009, 29:4373-4380.
49. Zandecki M., Laï J.L., Facon T. Multiple myeloma: almost all patients are cytogenetically abnormal. Br. J. Haematol. 1996, 94:217-227.
50. Zhang J.H., Chung T.D., Oldenburg K.R. A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J.Biomol. Screen. 1999, 4:67-73.
51. Zlei M., Egert S., Wider D., Ihorst G., Wäsch R., Engelhardt M. Characterization of invitro growth of multiple myeloma cells. Exp. Hematol. 2007, 35:1550-1561.