Ras/Raf signalling and emerging pharmacotherapeutic targets

Expert Opinion on Pharmacotherapy

Volumn 3, Issue 6, 2002, Pages 709-718

  Kolch, Walter ^a  

^a BEATSON INSTITUTE FOR CANCER RESEARCH   (United Kingdom)

Author keywords

Antisense; Apoptosis; Cancer differentiation; ERK; Isoprenylation; Kinase inhibitor; Knockout mouse; MAPK; MEK; MEK inhibitors; Protein interactions; Raf; Raf inhibitors; Ras; Ras inhibitors; Transformation

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; 2 (2 CHLORO 4 IODOANILINO) N CYCLOPROPYLMETHOXY 3,4 DIFLUOROBENZAMIDE; ANTINEOPLASTIC AGENT; ANTISENSE OLIGONUCLEOTIDE; APTAMER; CGP 69846A; CISPLATIN; FARNESYL TRANS TRANSFERASE; FR 901228; GELDANAMYCIN; GEMCITABINE; L 779450; LACTONE DERIVATIVE; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; MITOMYCIN; N [5 (3 DIMETHYLAMINOBENZAMIDO) 2 METHYLPHENYL] 4 HYDROXYBENZAMIDE; OXINDOLE; PACLITAXEL; PHOSPHOTRANSFERASE INHIBITOR; PROTEIN FARNESYLTRANSFERASE INHIBITOR; RAF PROTEIN; RAS PROTEIN; RIBOZYME; RO 09 2210; SORAFENIB; SULINDAC; TRANSFERASE INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; CANCER VACCINE; ENZYME INHIBITOR; MAP3K1 PROTEIN, HUMAN; MITOGEN ACTIVATED PROTEIN KINASE KINASE KINASE 1; PROTEIN SERINE THREONINE KINASE;

ANIMAL MODEL; CANCER; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL SURVIVAL; CLINICAL TRIAL; DEREGULATION; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENTIATION; DRUG TARGETING; DRUG TOLERANCE; HUMAN; HUMAN TISSUE; ISOPRENYLATION; NONHUMAN; ONCOGENE; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; VACCINATION; ANIMAL; CELL DIVISION; DRUG ANTAGONISM; DRUG EFFECT; GENETICS; METABOLISM; PHYSIOLOGY; PROTEIN PROCESSING;

ANIMALS; ANTINEOPLASTIC AGENTS; CANCER VACCINES; CELL DIVISION; CLINICAL TRIALS; ENZYME INHIBITORS; HUMANS; MAP KINASE KINASE KINASE 1; MAP KINASE SIGNALING SYSTEM; MITOGEN-ACTIVATED PROTEIN KINASES; OLIGONUCLEOTIDES, ANTISENSE; PROTEIN ISOPRENYLATION; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS C-RAF; RAS PROTEINS;

EID: 0036072924     PISSN: 14656566     EISSN: None     Source Type: Journal    
DOI: 10.1517/14656566.3.6.709     Document Type: Review

References (71)

1. Mitogen-activated protein (MAP) kinase pathways: Regulation and physiological functions
2. Signal transduction through MAPK cascades
3. RasGRP, a Ras guanyl nucleotide-releasing protein with calcium- and diacylglycerol-binding motifs
4. Regulation of Raf-1 activation and signalling by dephosphorylation
5. Meaningful relationships: The regulation of the Ras/Raf/MEK/ERK pathway by protein interactions
6. Ras activation of the Raf kinase: Tyrosine kinase recruitment of the MAPK cascade
7. Specificity of receptor tyrosine kinase signalling: Transient versus sustained extracellular signal-regulated kinase activation
8. Cooperating oncogenes converge to regulate cyclin/cdk complexes
9. Raf-1 without MEK?
10. Cell type specific integration of cross-talk between extracellular signal-regulated kinase and cAMP signalling
11. Extracellular signal Regulated Kinase (ERK)/Mitogen Activated Protein Kinase (MAPK) independent functions of Raf kinases
12. Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene
13. MEK kinase activity is not necessary for Raf-1 function
14. Uncoupling Raf1 from MEK1/2 impairs only a subset of cellular responses to Raf activation
15. SDF-1-induced activation of ERK enhances HIV-1 expression
16. Influenza virus propagation is impaired by inhibition of the Raf/MEK/ERK signalling cascade
17. PD98059 prevents neurite degeneration induced by fibrillar beta-amyloid in mature hippocampal neurons
18. Prevention of vasospasm in penetrating arteries with MAPK inhibitors in dog double-hemorrhage model
19. Activation of protein kinase cascades in the heart by hypertropic G protein-coupled receptor agonists
20. Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signalling pathway in human tumours
21. Blocking oncogenic Ras signalling for cancer therapy
22. Nonpeptidic prenyltransferase inhibitors: Diverse structural classes and surprising anticancer mechanisms
23. Farnesyltransferase and geranyl-geranyltransferase I inhibitors and cancer therapy: Lessons from mechanism and bench-to-bedside translational studies
24. K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors
25. Evaluation of farnesyl:Protein transferase and geranylgeranyl:Protein transferase inhibitor combinations in preclinical models
26. Both farnesyltransferase and geranylgeranyltransferase I inhibitors are required for inhibition of oncogenic K-Ras prenylation but each alone is sufficient to suppress human tumour growth in nude mouse xenografts
27. Farnesyltransferase inhibitors: Mechanism and applications
28. Current status of clinical trials of farnesyltransferase inhibitors
29. Antitumour efficacy of a novel class of nonthiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase I: Combination therapy with the cytotoxic agents cisplatin, Taxol and gemcitabine
30. Antisense therapeutics: Lessons from early clinical trials
31. A Phase I trial of H-ras antisense oligonucleotide ISIS 2503 administered as a continuous intravenous infusion in patients with advanced carcinoma
32. Suppression of the neoplastic phenotype in vivo by an antiras ribozyme
33. Specific hammerhead ribozyme-mediated cleavage of mutant N-ras mRNA in vitro and ex vivo. Oligoribonucleotides as therapeutic agents
34. Antitumorigenic effect of a K-ras ribozyme against human lung cancer cell line heterotransplants in nude mice
35. A Phase I vaccine trial with peptides reflecting ras oncogene mutations of solid tumours
36. The many faces of Ras: Recognition of small GTP-binding proteins
37. Sulindac sulfide inhibits Ras signalling
38. New indenederivatives with antiproliferative properties
39. Synthesis and biological evaluation of cycloalkylidene carboxylic acids as novel effectors of ras/raf interaction
40. Peptides containing a consensus Ras binding sequence from Raf-1 and the GTPase activating protein NF1 inhibit Ras function
41. Selection of phage-displayed fab antibodies on the active conformation of ras yields a high affinity conformation-specific antibody preventing the binding of c-Raf kinase to Ras
42. Anti(Raf-1) RNA aptamers that inhibit Ras-induced Raf-1 activation
43. Reovirus therapy of tumours with activated Ras pathway
44. Reovirus oncolysis of human breast cancer
45. Viruses as therapeutic agents against malignant disease of the central nervous system
46. The role of Raf kinases in malignant transformation
47. The Raf signal transduction cascade as a target for chemotherapeutic intervention in growth factor-responsive tumours
48. Paradoxical activation of Raf by a novel Raf inhibitor
49. A prodrug approach to the design of cRaf1 kinase inhibitors with improved cellular activity
50. Identification of potent, selective inhibitors of Raf
51. Discovery of a novel Raf kinase inhibitor
52. Phase I Trial of ISIS 5132, an antisense oligonucleotide inhibitor of c-raf 1, administered by 24-hour weekly infusion to patients with advanced cancer
53. Toward antisense oligonucleotide therapy for cancer: ISIS compounds in clinical development
54. Exposure of human vascular smooth muscle cells to Raf-1 antisense oligodeoxynucleotides: Cellular responses and pharmacodynamic implications
55. Inhibition of C-raf expression by antisense oligonucleotides extends heart allograft survival in rats
56. HSP90 as a new therapeutic target for cancer therapy: The story unfolds
57. Inhibitor of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T cell lymphoma: A case report
58. PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo
59. Identification of a novel inhibitor of mitogen-activated protein kinase kinase
60. Blockade of the MAPK pathway suppresses growth of colon tumours in vivo
61. Determinants of sensitivity to MAPK pathway intervention by MEK inhibition
62. Effects of MAPK cascade inhibitors on the MKK5/ERK5 pathway
63. Synthesis and structure-activity relationships of 3-cyano-4-(phenoxyanilino)quinolines as MEK (MAPKK) inhibitors
64. Resorcylic acid lactones: Naturally-occurring potent and selective inhibitors of MEK
65. Ro 09-2210 exhibits potent antiproliferative effects on activated T cells by selectively blocking MKK activity
66. Suppression of Raf-1 kinase activity and MAPK signalling by RKIP
67. Selective Grb2 SH2 inhibitors as antiRas therapy
68. Suppression of Ras-mediated transformation and inhibition of tumour growth and angiogenesis by anthrax lethal factor, a proteolytic inhibitor of multiple MEK pathways
69. Nuclear translocation of p42/p44 mitogen-activated protein kinase is required for growth factor-induced gene expression and cell cycle entry
70. Measurement of MAPK activation by flow cytometry using phospho-specific antibodies to MEK and ERK: Potential for pharmacodynamic monitoring of signal transduction inhibitors