Real-time nanoscale proteomic analysis of the novel multi-kinase pathway inhibitor rigosertib to measure the response to treatment of cancer

Expert Opinion on Investigational Drugs

Volumn 22, Issue 11, 2013, Pages 1495-1509

  Fan, Alice C ^a   O'Rourke, Jennifer J ^a   Praharaj, Dave R ^a   Felsher, Dean W ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

DNA methyl transferase inhibitors; Myelodysplastic syndromes; Nanoimmunoassay; ON 01910.Na; Phosphatidylinositol 3 kinase; Polo like kinase; Rigosertib

Indexed keywords

CASPASE 3; CYCLIN D1; DOXORUBICIN; GEMCITABINE; MITOGEN ACTIVATED PROTEIN KINASE; MYC PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; POLO LIKE KINASE 1; PROTEIN BCL 2; PROTEIN KINASE B BETA; RIGOSERTIB; SCATTER FACTOR RECEPTOR; STAT PROTEIN; STAT3 PROTEIN; STRESS ACTIVATED PROTEIN KINASE; SURVIVIN;

ABDOMINAL PAIN; ANEMIA; ANTINEOPLASTIC ACTIVITY; ARTICLE; BONE PAIN; CANCER SIZE; CANCER SURVIVAL; CENTROSOME; DEFECATION URGENCY; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG HALF LIFE; DRUG RESPONSE; FATIGUE; HUMAN; IN VITRO STUDY; LIVER CELL CARCINOMA; M PHASE CELL CYCLE CHECKPOINT; MAXIMUM TOLERATED DOSE; MITOSIS SPINDLE; MULTICENTER STUDY (TOPIC); MULTIPLE CYCLE TREATMENT; MYELODYSPLASTIC SYNDROME; NAUSEA; NEUTROPENIA; NONHUMAN; OVARY CANCER; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN PHOSPHORYLATION; PROTEOMICS; QUALITY OF LIFE; SOLID TUMOR; THROMBOCYTOPENIA; TREATMENT RESPONSE; TUMOR REGRESSION;

ANTINEOPLASTIC AGENTS; BIOLOGICAL MARKERS; GLYCINE; HUMANS; MYELODYSPLASTIC SYNDROMES; NANOTECHNOLOGY; NEOPLASMS; PROTEIN KINASE INHIBITORS; PROTEOMICS; SULFONES; TREATMENT OUTCOME;

EID: 84885736975     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2013.829453     Document Type: Article

References (76)

1. Albert S, Serova M, Dreyer C, et al. New inhibitors of the mammalian target of rapamycin signaling pathway for cancer. Expert Opin Investig Drugs 2010;19(8):919-30
2. Bachireddy P, Rakhra K, Felsher DW. Immunology in the clinic review series; focus on cancer: multiple roles for the immune system in oncogene addiction. Clin Exp Immunol 2012;167(2):188-94
3. Bruserud O, Reikvam H. Therapeutic targeting of NF-kappaB in myelodysplastic syndromes and acute myeloid leukaemia - the biological heterogeneity. Expert Opin Ther Targets 2010;14(11):1139-42
4. Casey SC, Bellovin DI, Felsher DW. Noncanonical roles of the immune system in eliciting oncogene addiction. Curr Opin Immunol 2013;25(2):246-58
5. Choi PS, van Riggelen J, Gentles AJ, et al. Lymphomas that recur after MYC suppression continue to exhibit oncogene addiction. Proc Natl Acad Sci USA 2011;108(42):17432-7
6. Felsher DW. MYC Inactivation elicits oncogene addiction through both tumor cell-intrinsic and host-dependent mechanisms. Genes Cancer 2010;1(6):597-604
7. Felsher DW, Bishop JM. Reversible tumorigenesis by MYC in hematopoietic lineages. Mol Cell 1999;4(2):199-207
8. Jain M, Arvanitis C, Chu K, et al. Sustained loss of a neoplastic phenotype by brief inactivation of MYC. Science 2002;297(5578):102-4
9. Patel S, Player MR. Small-molecule inhibitors of the p53-HDM2 interaction for the treatment of cancer. Expert Opin Investig Drugs 2008;17(12):1865-82 . This work illustrates that FACS based analysis can identify specific changes in phophoproteins in response to rigosertib.
10. Reikvam H, Hatfield KJ, Lassalle P, et al. Targeting the angiopoietin (Ang)/Tie-2 pathway in the crosstalk between acute myeloid leukaemia and endothelial cells: Studies of Tie-2 blocking antibodies, exogenous Ang-2 and inhibition of constitutive agonistic Ang-1 release. Expert Opin Investig Drugs 2010;19(2):169-83
11. Reikvam H, Nepstad I, Sulen A, et al. Increased antileukemic effects in human acute myeloid leukemia by combining HSP70 and HSP90 inhibitors. Expert Opin Investig Drugs 2013;22(5):551-63
12. Shachaf CM, Kopelman AM, Arvanitis C, et al. MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 2004;431(7012):1112-17
13. Stapnes C, Gjertsen BT, Reikvam H, Bruserud O. Targeted therapy in acute myeloid leukaemia: Current status and future directions. Expert Opin Investig Drugs 2009;18(4):433-55
14. Tsykunova G, Reikvam H, Ahmed AB, et al. Targeting of polo-like kinases and their cross talk with Aurora kinases-possible therapeutic strategies in human acute myeloid leukemia? Expert Opin Investig Drugs 2012;21(5):587-603
15. Lee JT, Li L, Brafford PA, et al. PLX4032, a potent inhibitor of the B-Raf V600E oncogene, selectively inhibits V600E-positive melanomas. Pigment Cell Melanoma Res 2010;23(6):820-7
16. Smalley KS. PLX-4032, a small-molecule B-Raf inhibitor for the potential treatment of malignant melanoma. Curr Opin Investig Drugs 2010;11(6):699-706
17. Cortes JE, Baccarani M, Guilhot F, et al. Phase III, randomized, open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase using molecular end points: Tyrosine kinase inhibitor optimization and selectivity study. J Clin Oncol 2010;28(3):424-30
18. Hughes T, Deininger M, Hochhaus A, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: Review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 2006;108(1):28-37
19. Druker BJ. Inhibition of the Bcr-Abl tyrosine kinase as a therapeutic strategy for CML. Oncogene 2002;21(56):8541-6
20. Reddy MVR, Venkatapuram P, Mallireddigari MR, et al. Discovery of a Clinical Stage Multi-Kinase Inhibitor Sodium (E)-2-{2-Methoxy-5-[(2¢, 4¢,6¢- trimethoxystyrylsulfonyl)methyl] phenylamino} acetate (ON 01910.Na): Synthesis, Structure-Activity Relationship, and Biological Activity. J Med Chem 2011;54(18):6254-76
21. Seetharam M, Fan AC, Tran M, et al. Treatment of higher risk myelodysplastic syndrome patients unresponsive to hypomethylating agents with ON 01910. Na. Leuk Res 2012;36(1):98-103 .. The authors provide the first in vivo clinical evidence that rigosertib has clinical efficacy in patients with myelodysplaisa.
22. Fan AC, Deb-Basu D, Orban MW, et al. Nanofluidic proteomic assay for serial analysis of oncoprotein activation in clinical specimens. Nat Med 2009;15(5):566-71 . This manuscript provided the first in vivo evidence that nanoscale immunoassay could be used to examine therapeutic activity in human patients.
23. DeChristopher BA, Fan AC, Felsher DW, Wender PA. "Picolog," a synthetically-available bryostatin analog, inhibits growth of MYC-induced lymphoma in vivo. Oncotarget 2012;3(1):58-66
24. Xin HW, Ambe CM, Hari DM, et al. Label-retaining liver cancer cells are relatively resistant to sorafenib. Gut 2013; [Epub ahead of print]
25. O?Neill RA, Bhamidipati A, Bi X, et al. Isoelectric focusing technology quantifies protein signaling in 25 cells. Proc Natl Acad Sci USA 2006;103(44):16153-8 .. This is the first description of the use of a novel nanoscale microfluidic technology to measure protein quantity and phosphorylation using picograms of material.
26. Kedei N, Telek A, Czap A, et al. The synthetic bryostatin analog Merle 23 dissects distinct mechanisms of bryostatin activity in the LNCaP human prostate cancer cell line. Biochem Pharmacol 2011;81(11):1296-308
27. Kentsis A, Reed C, Rice KL, et al. Autocrine activation of the MET receptor tyrosine kinase in acute myeloid leukemia. Nat Med 2012;18(7):1118-22
28. Sun Z, Li X, Massena S, et al. VEGFR2 induces c-Src signaling and vascular permeability in vivo via the adaptor protein TSAd. J Exp Med 2012;209(7):1363-77
29. Le Grand F, Grifone R, Mourikis P, et al. Six1 regulates stem cell repair potential and self-renewal during skeletal muscle regeneration. J Cell Biol 2012;198(5):815-32
30. Drew DA, Devers T, Horelik N, et al. Nanoproteomic analysis of extracellular receptor kinase-1/2 post-translational activation in microdissected human hyperplastic colon lesions. Proteomics 2013;13(9):1428-36
31. Goff DJ, Recart AC, Sadarangani A, et al. A Pan-BCL2 inhibitor renders bone-marrow-resident human leukemia stem cells sensitive to tyrosine kinase inhibition. Cell Stem Cell 2013;12(3):316-28
32. Bentley C, Jurinka SS, Kljavin NM, et al. A requirement for WT Ras Isoforms in mutant KRas-driven signaling and transformation. Biochem J 2013;452(2):313-20
33. de Kreuk BJ, Anthony EC, Geerts D, Hordijk PL. The F-BAR protein PACSIN2 regulates epidermal growth factor receptor internalization. J Biol Chem 2012;287(52):43438-53
34. Beurlet S, Omidvar N, Krief P, et al. BCL-2 inhibition with ABT-737 prolongs survival in an NRAS/BCL-2 mouse model of myeloid leukemia by targeting leukemia initiating cells. Blood 2013; In press
35. Fan AC, Leppert J, Liliental JE, et al. Nanoscale proteomic profiling to define diagnostic signatures and biomarkers of therapeutic activity in patients with RCC. ASCO GU; 2013
36. Fan AC, Leppert J, Liliental JE, et al. Nano-scale proteomic profiles of response to targeted therapy in patients with RCC. AACR; 2013
37. Oussenko IA, Holland JF, Reddy EP, Ohnuma T. Effect of ON 01910.Na, an anticancer mitotic inhibitor, on cell-cycle progression correlates with RanGAP1 hyperphosphorylation. Cancer Res 2011;71(14):4968-76 . The authors illustrate that rigosertib has discrete biological activity associated with discrete effects on cell cycle progression.
38. Oussenko I, Holland JF, Reddy EP, Ohnuma T. RanGAP1.SUMO1 hyperphosphorylation (RGSH) and mitotic arrest by ON 01910.Na, okadaic acid or tubulin agents (abstract #2639). Proc AAPS Annual Meeting; 2011
39. Gumireddy K, Reddy MV, Cosenza SC, et al. ON01910, a non-ATP-competitive small molecule inhibitor of Plk1, is a potent anticancer agent. Cancer Cell 2005;7(3):275-86
40. Prasad A, Park IW, Allen H, et al. Styryl sulfonyl compounds inhibit translation of cyclin D1 in mantle cell lymphoma cells. Oncogene 2009;28(12):1518-28
41. Sumara I, Gimenez-Abian JF, Gerlich D, et al. Roles of polo-like kinase 1 in the assembly of functional mitotic spindles. Curr Biol 2004;14(19):1712-22
42. Renner AG, Dos Santos C, Recher C, et al. Polo-like kinase 1 is overexpressed in acute myeloid leukemia and its inhibition preferentially targets the proliferation of leukemic cells. Blood 2009;114(3):659-62
43. Liu X, Erikson RL. Polo-like kinase (Plk) 1 depletion induces apoptosis in cancer cells. Proc Natl Acad Sci USA 2003;100(10):5789-94 . This paper provides compelling evidence for the importance of Plk1 to the survival programs of cancer cells.
44. Guan R, Tapang P, Leverson JD, et al. Small interfering RNA-mediated Pololike kinase 1 depletion preferentially reduces the survival of p53-defective, oncogenic transformed cells and inhibits tumor growth in animals. Cancer Res 2005;65(7):2698-704
45. Chapman CM, Sun X, Roschewski M, et al. ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Clin Cancer Res 2012;18(7):1979-91
46. Reddy MV, Venkatapuram P, Mallireddigari MR, et al. Discovery of a clinical stagemulti-kinaseinhibitorsodium (E)-2-{2-methoxy-5-[(2¢,4¢, 6¢- trimethoxystyrylsulfonyl)methyl] phenylamino}acetate (ON 01910.Na): Synthesis, structure-activity relationship, and biological activity. J Med Chem 2011;54(18):6254-76
47. Jimeno A, Rubio-Viqueira B, Rajeshkumar NV, et al. A fine-needle aspirate-based vulnerability assay identifies polo-like kinase 1 as a mediator of gemcitabine resistance in pancreatic cancer. Mol Cancer Ther 2010;9(2):311-18
48. Taft DR, Dave R, Gillum AM, Maniar M. ON 01910.Na. Drugs Future 2011;36(6):433-40
49. Olnes MJ, Shenoy A, Weinstein B, et al. Directed therapy for patients with myelodysplastic syndromes (MDS) by suppression of cyclin D1 with ON 01910.Na. Leuk Res 2012;36(8):982-9
50. Skidan I, Zinzar S, Holland JF, et al. Toxicology of a novel small molecule ON 01910.Na on human bone marrow and leukemic cells in vitro. AACR Annual Meeting. Proc AmAssoc Cancer Res 2006;47:abstract #1310
51. Chen G, Zeng W, Miyazato A, et al. Distinctive gene expression profiles of CD34 cells from patients with myelodysplastic syndrome characterized by specific chromosomal abnormalities. Blood 2004;104(13):4210-18
52. Sloand EM, Pfannes L, Reddy MVR, et al. Suppression of Cyclin D1 by on 01910.Na is associated with decreased survival of trisomy 8 myelodysplastic bone marrow progenitors: A potential targeted therapy. ASH Annual Meeting. Blood 2007;110:abstract #822
53. Walter MJ, Shen D, Ding L, et al. Clonal architecture of secondary acute myeloid leukemia. N Engl J Med 2012;366(12):1090-8
54. Jimeno A, Li J, Messersmith WA, et al. Phase I study of ON 01910.Na, a novel modulator of the Polo-like kinase 1 pathway, in adult patients with solid tumors. J Clin Oncol 2008;26(34):5504-10 . This study illustrates the potential activity of rigosertib in patients with solid malignanices.
55. Jimeno A, Chan A, Cusatis G, et al. Evaluation of the novel mitotic modulator ON 01910.Na in pancreatic cancer and preclinical development of an ex vivo predictive assay. Oncogene 2009;28(4):610-18 . This study suggests that rigosertin has activity in pancreatic cancer associated with specific biomarkers.
56. Jimeno A, Wheelhouse J, Chan F, et al. A gene expression-based approach to devise combinations with gemcitabine (GEM) in pancreatic cancer (PC) identifies polo-like kinase 1 (Plk1) as a rational target. Proc Amer Assoc Cancer Res 2008;49:abstract #1597
57. Ma WW, Messersmith WA, Dy GK, et al. Phase I study of rigosertib, an inhibitor of the phosphatidylinositol 3-Kinase and polo-like kinase 1 pathways, combined with gemcitabine in patients with solid tumors and pancreatic cancer. Clin Cancer Res 2012;18(7):2048-55
58. Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 2006;108(2):419-25
59. Cheson BD, Bennett JM, Kantarjian H, et al. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood 2000;96(12):3671-4
60. Kern W, Haferlach T, Schoch C, et al. Early blast clearance by remission induction therapy is a major independent prognostic factor for both achievement of complete remission and long-term outcome in acute myeloid leukemia: data from the German AML Cooperative Group (AMLCG) 1992 Trial. Blood 2003;101(1):64-70
61. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood 2012;120(12):2454-65
62. Olnes MJ, Shenoy A, Weinstein B, et al. Directed therapy for patients with myelodysplastic syndromes (MDS) by suppression of cyclin D1 with ON 01910.Na. Leukemia Res 2012;36(8):982-9
63. Cesano A, Soper DM, Banville S, et al. Single-cell network profiling (SCNP) to evaluate the proteomic profiles associated with ON 01910.Na treatment of MDS patients (Pts). AACR Annual Meeting 2011;71:abstract #4136 . This work illustrates that FACS based analysis can identify specific changes in phophoproteins in response to rigosertib.
64. Jimeno A, Bowles D, Aisner D, et al. editors. Phase I and molecular correlates of oral rigosertib in patients with refractory metastatic head and neck cancer and advanced solid tumors. AACR Annual Meeting; Washington DC; 2013
65. Ghalib M, Weinstein J, Maniar M, et al. ON01910.Na, a novel polo-like kinase pathway modulator as a treatment for patients with advanced cancer. AACR Annual Meeting. Proc Am Assoc Cancer Res 2008;49:abstract #5652
66. Chaudhary I, Rajdev L, Swami U, et al. Phase I dose-escalation study Of ON 01910.Na in combination with oxaliplatin in patients with advanced solid tumors. ASCO Annual Meeting. J Clin Oncol 2010;28:e13133
67. Navada SC, Odchimar-Reissig R, Reddy EP, et al. Evaluation of rigosertib in patients with a Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) relapsed or refractory to hypomethylating agents: A phase I/II study. ASH Annual Meeting, Atlanta, GA. Blood 2012;120:abstract #3794
68. Raza A, Galili N, Ali MS, et al. Initial evaluation of a 48-h continuous intravenous infusion weekly regimen of ON 01910.Na in advanced Myelodysplastic Syndrome (MDS). ASH Annual Meeting, New Orleans, LA. Blood 2009;114:abstract #3815
69. Roschewski M, Farooqui M, Aue G, et al. Phase I study of ON 01910.Na (Rigosertib), a multikinase PI3K inhibitor in relapsed/refractory B-cell malignancies. ASH Annual Meeting, Atlanta, GA. Blood 2012;120:abstract #1803
70. Katragadda L, Kantarjian H, Garcia-Manero G, et al. Phase1/2 single arm study of rigosertib (ON 01910.Na) In Patients (Pts) with relapsed or refractory acute Leukemia or transformed myeloproliferative neoplasms. ASH Annual Meeting, Atlanta, GA. Blood 2012;120:abstract #3606
71. Bowles DW, Diamond J, Lam E, et al. Phase I study of oral rigosertib in patients with advanced solid tumors. ASCO Annual Meeting, Chicago, IL. J Clin Oncol 2012;30(SUPPL.):abstract #3017
72. Raza A, Komrokji RS, Brooks R, et al. A phase 1 study to assess oral bioavailability of a novel oral soft gelatin capsule formulation of rigosertib (ON 01910.Na) under fasted and fed conditions in patients with myelodysplastic syndromes. ASCO Annual Meeting, Chicago, IL. J Clin Oncol 2012;30(SUPPL.): abstract #3081
73. Komrokji RS, Raza A, Lancet JE, et al. Phase I clinical trial of oral rigosertib in patients with myelodysplastic syndromes. Br J Haematol 2013;162(4):517-24
74. Raza A, Mukherjee S, Eisenberger A, et al. Phase II study of orally administered rigosertib (ON 01910.Na) in transfusion-dependent lower-risk myelodysplastic syndrome (MDS) patients. J Clin Oncol 2013;31(SUPPL.):abstract 7031
75. Ohnuma T, Holland JF, Goel S, et al. Final results of a phase 1 dose-escalation study of ON 01910.Na in combination with oxaliplatin in patients with advanced solid tumors. J Clin Oncol 2011;29(SUPPL.):abstract e13584
76. Ohnuma T, Lehrer D, Ren C, et al. Phase 1 study of intravenous rigosertib (ON 01910.Na), a novel benzyl styryl sulfone structure producing G2/M arrest and apoptosis, in adult patients with advanced cancer. Am J Cancer Res 2013;3(3):323-38