A phase II study of the Ras-MAPK signaling pathway inhibitor TLN-4601 in patients with glioblastoma at first progression

Journal of Neuro-Oncology

Volumn 107, Issue 2, 2012, Pages 343-349

  Mason, Warren P ^a   Belanger, Karl ^b   Nicholas, Garth ^c   Vallières, Isabelle ^d   Mathieu, David ^e   Kavan, Petr ^f   Desjardins, Annick ^g   Omuro, Antonio ^h   Reymond, Didier ⁱ  

^a PRINCESS MARGARET HOSPITAL   (Canada)

^b NOTRE DAME HOSPITAL   (Canada)

^c OTTAWA REGIONAL CANCER CENTRE   (Canada)

^d LAVAL UNIVERSITY   (Canada)

^e CENTRE HOSPITALIER UNIVERSITAIRE DE SHERBROOKE   (Canada)

^f ROYAL VICTORIA HOSPITAL   (Canada)

^g DUKE UNIVERSITY MEDICAL CENTER   (United States)

^h MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

ⁱ Thallion Pharmaceuticals Inc   (Canada)

Author keywords

Anticancer agent; Glioblastoma; Raf 1; Ras MAPK signaling pathway; TLN 4601

Indexed keywords

ANTINEOPLASTIC AGENT; DIAZEPINOMICIN; DIBENZAZEPINE DERIVATIVE; EGFR PROTEIN, HUMAN; EPIDERMAL GROWTH FACTOR RECEPTOR; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PTEN PROTEIN, HUMAN;

ADULT; AGED; ARTICLE; BLOOD; BRAIN TUMOR; CLINICAL TRIAL; DRUG EFFECT; FEMALE; FOLLOW UP; GENE EXPRESSION REGULATION; GLIOBLASTOMA; HUMAN; INTRACEREBROVENTRICULAR DRUG ADMINISTRATION; KAPLAN MEIER METHOD; LIQUID CHROMATOGRAPHY; MALE; METABOLISM; MIDDLE AGED; MORTALITY; MULTICENTER STUDY; NUCLEAR MAGNETIC RESONANCE IMAGING; PHASE 2 CLINICAL TRIAL; TANDEM MASS SPECTROMETRY;

ADULT; AGED; ANTINEOPLASTIC AGENTS; BRAIN NEOPLASMS; CHROMATOGRAPHY, LIQUID; DIBENZAZEPINES; FEMALE; FOLLOW-UP STUDIES; GENE EXPRESSION REGULATION, NEOPLASTIC; GLIOBLASTOMA; HUMANS; INFUSIONS, INTRAVENTRICULAR; KAPLAN-MEIER ESTIMATE; MAGNETIC RESONANCE IMAGING; MALE; MIDDLE AGED; PTEN PHOSPHOHYDROLASE; RECEPTOR, EPIDERMAL GROWTH FACTOR; TANDEM MASS SPECTROMETRY;

EID: 84863595655     PISSN: 0167594X     EISSN: 15737373     Source Type: Journal    
DOI: 10.1007/s11060-011-0747-6     Document Type: Article

References (18)

1. CBTRUS (2011) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2004-2007. Central brain tumor registry of the United States, Hinsdale, IL
2. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459-466. doi:10.1016/S1470-2045(09)70025-7
3. Boufaied N, Wioland M-A, Falardeau P, Gourdeau H (2010) TLN-4601, a novel anticancer agent, inhibits Ras signaling post Ras prenylation and before MEK activation. Anti-Cancer Drugs 21:543-552
4. Gourdeau H, McAlpine JB, Ranger M, Simard B, Berger F, Beaudry F, Farnet CM, Falardeau P (2008) Identification, characterization and potent antitumor activity of ECO-4601, a novel peripheral benzodiazepine receptor ligand. Cancer Chemother Pharmacol 61:911-921. doi:10.1007/s00280-007-0544-2
5. Campbell PM, Boufaied N, Fiordalisi JJ, Cox AD, Falardeau P, Der CJ, Courdeau H (2010) TLN-4601 suppresses growth and induces apoptosis of pancreatic carcinoma cells through inhibition of Ras-ERK MAPK signaling. J Mol Signal 5:18
6. Bertomeu T, Zvereff V, Ibrahim A, Zehntner SP, Aliaga A, RosoNeto P, Bedell BJ, Falardeau P, Gourdeau H (2010) TLN-4601 peripheral benzodiazepine receptor (PBR/TSPO) binding properties do not mediate apoptosis but confer tumor-specific accumulation. Biochem Pharmacol 80:1572-1579
7. Olson JMM, Junck L, Young AB, Penney JB, Mancini WR (1988) Isoquinoline and peripheral-type benzodiazepine binding in gliomas: implications for diagnostic imaging. Cancer Res 48:5837-5841
8. Duerr EM, Rollbrocker B, Hayashi Y, Peters N, Meyer-Puttlitz B, Louis DN, Schramm J, Wiestler OD, Parsons R, Eng C, von Deimling A (1998) PTEN mutations in gliomas and glioneuronal tumors. Oncogene 16:2259-2264. doi:10.1038/sj.onc. 1201756
9. Ohgaki H, Kleihues P (2007) Genetic pathways to primary and secondary glioblastoma. Am J Pathol 170:1445-1453. doi: 10.2353/ajpath.2007.070011
10. Louis DN (2006) Molecular pathology of malignant gliomas. Annu Rev Pathol 1:97-117. doi:10.1146/annurev.pathol.1.110304. 100043
11. Guha A, Feldkamp MM, Lau N, Boss G, Pawson A (1997) Proliferation of human malignant astrocytomas is dependent on Ras activation. Oncogene 15:2755-2765
12. Woods SA, Marmor E, Feldkamp M, Lau N, Apicelli AJ, Boss G, Gutmann DH, Guha A (2002) Aberrant G protein signaling in nervous system tumors. J Neurosurg 97:627-642. doi:10.3171/jns.2002.97.3.0627
13. Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277-1280
14. Chow S, Patel H, Hedley DW (2001) Measurement of MAP kinase activation by flow cytometry using phospho-specific antibodies to MEK and ERK: potential for pharmacodynamic monitoring of signal transduction inhibitors. Cytometry 46: 72-78. doi:10.1002/cyto
15. Camsonne R, Crouzel C, Comar D, Maziere M, Prenant C, Sastre J, Moulin M, Syrota A (1984) Synthesis of N-(11C)methyl, N-(1methylpropyl), 1-(2-chlorophenyl)isoquinoleine carboxamide-3 (PK11195): a new ligand for peripheral benzodiaepine receptors. J Label Compd Radiopharm 21:985-991
16. Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:481-547
17. Abounader R (2009) Interactions between PTEN and receptor tyrosine kinase pathways and their implications for glioma therapy. Expert Rev Anticancer Ther 9:235-245. doi:10.1586/1473 7140.9.2.235
18. Kondo Y, Hollingsworth EF, Kondo S (2004) Molecular targeting for malignant gliomas (Review). Int J Oncol 24:1101-1109