Selected novel anticancer treatments targeting cell signaling proteins

Oncologist

Volumn 6, Issue 6, 2001, Pages 517-537

  Elsayed, Yusri A ^a   Sausville, Edward A ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Cell cycle; Chemotherapy; Cyclin dependent kinase; Histone deacetylase inhibitor; Proteasome inhibitor; Tyrosine kinase inhibitor

Indexed keywords

7 HYDROXYSTAUROSPORINE; ALPHA INTERFERON; ANTINEOPLASTIC AGENT; BORTEZOMIB; CARBOPLATIN; CETUXIMAB; CISPLATIN; CYCLOPHOSPHAMIDE; CYTARABINE; DEPSIPEPTIDE; DOCETAXEL; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR ANTIBODY; ERLOTINIB; ETOPOSIDE; FLAVOPIRIDOL; FLUDARABINE; FR 901228; GEFITINIB; HISTONE DEACETYLASE INHIBITOR; HYDROXYUREA; IMATINIB; METHOTREXATE; MIDOSTAURIN; N (2 AMINOPHENYL) 4 (3 PYRIDINYLMETHOXYCARBONYLAMINOMETHYL)BENZAMIDE; OXALIPLATIN; PACLITAXEL; PROTEASOME INHIBITOR; TEMSIROLIMUS; TOPOTECAN; UNINDEXED DRUG; VINCRISTINE;

ARTICLE; CANCER; CANCER CHEMOTHERAPY; CELL CYCLE; CLINICAL TRIAL; DRUG INFUSION; DRUG MECHANISM; DRUG POTENTIATION; DRUG SCREENING; DRUG STRUCTURE; DRUG TARGETING; ENZYME INHIBITION; HUMAN; NONHUMAN; PRIORITY JOURNAL; TOXICITY; TREATMENT OUTCOME;

ANTINEOPLASTIC AGENTS; CELL CYCLE; CELL DIVISION; CYCLIN-DEPENDENT KINASES; ENZYME INHIBITORS; HUMANS; MUTATION; NEOPLASM PROTEINS; NEOPLASMS; PROTEIN ISOPRENYLATION; SIGNAL TRANSDUCTION;

EID: 0035215722     PISSN: 10837159     EISSN: None     Source Type: Journal    
DOI: 10.1634/theoncologist.6-6-517     Document Type: Article

References (189)

1. Cancer cell cycles
2. Cell cycle control and cancer
3. Abnormal cell cycle regulation in malignancy
4. Distinct roles for cyclin-dependent kinases in cell cycle control
5. The retinoblastoma protein and cell cycle control
6. Cell cycle control in eukaryotes: Molecular mechanisms of cdc2 activation
7. 1-phase progression
8. Inhibition of CDKs as a therapeutic modality
9. Principles of CDK regulation
10. p21 is a universal inhibitor of cyclin kinases
11. The regulation of E2F by pRB-family proteins
12. The role of RB in cell cycle control
13. 1 phase progression: Cycling on cue
14. Checkpoints: Controls that ensure the order of cell cycle events
15. Cell cycle molecular targets in novel anticancer drug discovery
16. Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age
17. Molecular foundations of cancer: New targets for intervention
18. 1 cyclins
19. Alterations of the cyclin D1/p16-pRB pathway in mantle cell lymphoma
20. Genetic alterations of cyclins, cyclindependent kinases, and Cdk inhibitors in human cancer
21. Amplification of cyclin genes in colorectal carcinomas
22. Cyclin D and oncogenesis
23. Expression of human herpesvirus 8-encoded cyclin D in Kaposi's sarcoma spindle cells
24. The role of cyclin E in cell proliferation, development and cancer
25. 1 cyclin that binds Cdk2 and is aberrantly expressed in human cancers
26. Expression and amplification of cyclin genes in human breast cancer
27. Modification of cyclin A expression by hepatitis B virus DNA integration in a hepatocellular carcinoma
28. Amplified CDK2 and cdc2 activities in primary colorectal carcinoma
29. Cyclin D, CDK4 and p16 expression in colorectal cancer [article in Japanese]
30. Cyclin-dependent kinase 6 (CDK6) amplification in human gliomas identified using two-dimensional separation of genomic DNA
31. A cell cycle regulator potentially involved in genesis of many tumor types
32. Somatic mutations of the MTS (multiple tumor suppressor) 1/CDK41 (cyclindependent kinase-4 inhibitor) gene in human primary nonsmall cell lung carcinomas
33. Rates of p 16 (MTS 1) mutations in primary tumors with 9p loss
34. Review of alterations of the cyclin-dependent kinase inhibitor INK4 family genes p15, p16, p18 and p19 in human leukemia-lymphoma cells
35. The molecular biology of esophageal carcinoma
36. Analysis of the p161NK4, p151NK4B genes abnormality and the amplification of cyclin D1 gene in esophageal cancer [article in Japanese]
37. Mutations of cell cycle regulators. Biological and clinical implications for human neoplasia
38. Expression of cellcycle regulators p27Kipl and cyclin E, alone and in combination, correlate with survival in young breast cancer patients
39. Decreased levels of the cell-cycle inhibitor p27Kipl protein: Prognostic implications in primary breast cancer
40. Reduced expression of the cell cycle inhibitor p27Kipl in non-small cell lung carcinoma: A prognostic factor independent of Ras
41. Increased proteasomedependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas
42. pp60(v-src) induction of cyclin D1 requires collaborative interactions between the extracellular signal-regulated kinase, p38, and Jun kinase pathways. A role for cAMP response element-binding protein and activating transcription factor-2 in pp60(v-src) signaling in breast cancer cells
43. Transforming p21 ras mutants and c-Ets-2 activate the cyclin D1 promoter through distinguishable regions
44. Cyclin D1/bcl-1 cooperates with myc genes in the generation of B-cell lymphoma in transgenic mice
45. Myc induces cyclin D1 expression in the absence of de novo protein synthesis and links mitogen-stimulated signal transduction to the cell cycle
46. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice
47. Cyclin D1 transgene impedes lymphocyte maturation and collaborates in lymphomagenesis with the myc gene
48. Overexpression of cyclin D1 correlates with recurrence in a group of forty-seven operable squamous cell carcinomas of the head and neck
49. Overexpression of cyclin D1 in human pancreatic carcinoma is associated with poor prognosis
50. Cyclin E overexpression as an independent risk factor of visceral relapse in breast cancer
51. The prognostic significance of altered cyclin-dependent kinase inhibitors in human cancer
52. Cyclin-dependent kinases: Initial approaches to exploit a novel therapeutic target
53. Small-molecule inhibitors of cyclin-dependent kinases: Molecular tools and potential therapeutics
54. Therapeutic potential of targeting the cell cycle
55. Chemical inhibitors of cyclin-dependent kinases
56. CDK inhibition and cancer therapy
57. ATP-site directed inhibitors of cyclin-dependent kinases
58. Flavopiridol (L86-8275, NSC-649890), a new kinase inhibitor for tumor therapy
59. Growth inhibition with reversible cell cycle arrest of carcinoma cells by flavone L86-8275
60. Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression, and has potent antitumor activity in vivo against human leukemia and lymphoma xenografts
61. The novel cyclin-dependent kinase inhibitor flavopiridol downregulates Bcl-2 and induces growth arrest and apoptosis in chronic B-cell leukemia lines
62. Early induction of apoptosis in hematopoietic cell lines after exposure to flavopiridol
63. Flavopiridol: A cytotoxic flavone that induces cell death in noncycling A549 human lung carcinoma cells
64. 1 arrest with inhibition of cyclin-dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells
65. Potent inhibition of CDC2 kinase activity by the flavonoid L86-8275
66. Alteration of the phosphorylation state of p34cdc2 kinase by the flavone L86-8275 in breast carcinoma cells. Correlation with decreased H1 kinase activity
67. Down-regulation of cyclin D1 by transcriptional repression in MCF-7 human breast carcinoma cells induced by flavopiridol
68. Flavopiridol, a protein kinase inhibitor, down-regulates hypoxic induction of vascular endothelial growth factor expression in human monocytes
69. Novel small molecule alpha v integrin antagonists: Comparative anti-cancer efficacy with known angiogenesis inhibitors
70. Flavopiridol binds to duplex DNA
71. Cytotoxic synergy between flavopiridol (NSC 649890, L86-8275) and various antineoplastic agents: The importance of sequence of administration
72. In vitro evaluation of flavopiridol, a novel cell cycle inhibitor, in bladder cancer
73. Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms
74. Flavopiridol, a novel cyclin-dependent kinase inhibitor, in metastatic renal cancer: A University of Chicago Phase II Consortium study
75. Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma
76. A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer
77. Flavopiridol metabolism in cancer patients is associated with the occurrence of diarrhea
78. Flavopiridol, a novel cyclin-dependent kinase inhibitor, suppresses the growth of head and neck squamous cell carcinomas by inducing apoptosis
79. A phase I trial of I hour infusion of Flavopiridol (FLA), a novel cyclin-dependent kinase inhibitor, in patients with advanced neoplasms
80. Phase I clinical and pharmacokinetic trial of the cyclin-dependent kinase (CDK) inhibitor Flavopiridol
81. Phase II trial of Flavopiridol in metastatic colorectal cancer: Preliminary results
82. A phase IB clinical trial of the sequence dependent combination of paclitaxel (P) and cisplatin (C) with cyclin dependent kinase (CDK) inhibitor flavopiridol in patients with advanced solid tumors
83. Metabolism of the anticancer drug flavopiridol, a new inhibitor of cyclin dependent kinases, in rat liver
84. Possible mechanisms of diarrheal side effects associated with the use of a novel chemotherapeutic agent, flavopiridol
85. The cyclin dependent kinase inhibitor flavopiridol improves the response to CPT-11 and demonstrates cures in colon cancer Xenografts
86. Clinical trials referral resource. Clinical trials of flavopiridol
87. UCN-01 and UCN-02, new selective inhibitors of protein kinase CI. Screening, producing organism and fermentation
88. Antitumor activity of UCN-01, a selective inhibitor of protein kinase C, in murine and human tumor models
89. 1 phase accumulation induced by UCN-01 is associated with dephosphorylation of Rb and CDK2 proteins as well as induction of CDK inhibitor p21/Cipl/WAFI/Sdil in p53-mutated human epidermoid carcinoma A431 cells
90. Preclinical and clinical development of cyclin-dependent kinase modulators
91. Differential effects of UCN-01, staurosporine and CGP41 251 on cell cycle progression and CDC2/cyclin BI regulation in A431 cells synchronized at M phase by nocodazole
92. Apoptosis in 7-hydroxystaurosporine-treated T lymphoblasts correlates with activation of cyclin-dependent kinases 1 and 2
93. The Chk1 protein kinase and the Cdc25C regulatory pathways are targets of the anticancer agent UCN-01
94. The radiosensitizing agent 7-hydroxystaurosporine (UCN-01) inhibits the DNA damage checkpoint kinase hChk1
95. UCN-01 suppresses thymidylate synthase gene expression and enhances 5-fluorouracil-induccd apoptosis in a sequence-dependent manner
96. Enhancement of cisplatin-induced cytotoxicity by 7-hydroxystaurosporine (UCN-01), a new G2-checkpoint inhibitor
97. 2 checkpoint function in cancer cells with disrupted p53
98. UCN-01 suppresses E2FI mediated by ubiquitin-proteasome-dependent degradation
99. Cell cycle arrest and growth inhibition by the protein kinase antagonist UCN-01 in human breast carcinoma cells
100. Clinical pharmacology of UCN-01: Initial observations and comparison to preclinical models
101. Phase I trial of 72-hour continuous infusion UCN-01 in patients with refractory neoplasms
102. Unpredicted clinical pharmacology of UCN-01 caused by specific binding to human alphal-acid glycoprotein
103. Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C
104. A phase I/pharmacologic study of UCN-01 (UCN) in combination with 5-fluorouracil (F) in patients with advanced solid tumors
105. A phase I and pharmacologic study of UCN-01. A protein kinase C inhibitor
106. Modulation of clinical drug resistance in a B cell lymphoma patient by the protein kinase inhibitor 7-hydroxystaurosporine: Presentation of a novel therapeutic paradigm
107. Phase I trial of 7-hydroxystaurosporine (UCN-01) and Fludarabine phosphate (FAMP); In vivo evidence of UCN-01 induced apoptosis in CLL
108. Staurosporine inhibits phorbol 12-myristate 13-acetate- and insulin-stimulated translocation of GLUTI and GLUT4 glucose transporters in rat adipose cells
109. Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia
110. Structural mechanism for STI-571 inhibition of abelson tyrosine kinase
111. Effects of the bcr/abl kinase inhibitors AG957 and NSC 680410 on chronic myelogenous leukemia cells in vitro
112. In vivo eradication of human BCR/ABL-positive leukemia cells with an ABL kinase inhibitor
113. Intracranial inhibition of platelet-derived growth factor-mediated glioblastoma cell growth by an orally active kinase inhibitor of the 2-phenylaminopyrimidine class
114. The selective tyrosine kinase inhibitor STI571 inhibits small cell lung cancer growth
115. In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents
116. Efficacy of STI571, an abl tyrosine kinase inhibitor, in conjunction with other antileukemic agents against bcr-abl-positive cells
117. CGP57148B (STI-571) induces differentiation and apoptosis and sensitizes Bcr-Abl-positive human leukemia cells to apoptosis due to antileukemic drugs
118. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia
119. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome
120. STI571: Targeting BCR-ABL as therapy for CML
121. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor
122. STI571, an active drug in metastatic gastro intestinal stromal tumors (GIST), an EORTC phase I study
123. Epidermal growth factor-related peptides and their receptors in human malignancies
124. Prevalence of aberrant expression of the epidermal growth factor receptor in human cancers
125. Epidermal-growth-factor receptors in human bladder cancer: Comparison of invasive and superficial tumours
126. Differential expression of epidermal growth factor receptor in human head and neck cancers
127. Phase I studies of antiepidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin
128. Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase
129. Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor
130. Combination of ZD1839 ("Iressa"), an EGFR-TKI, and radiotherapy increases antitumor efficacy in a human colon cancer xenograft model
131. ZD 1839 (Iressa), an EGFR-TKI, and cisplatin have an additive effect on programmed cell death in human head and neck squamous carcinoma cells in vitro
132. Low dose cisplatin can modulate the sensitivity of human non-small cell lung carcinoma cells to EGFR tyrosine kinase inhibitor (ZD839; Iressa) in vivo
133. Antiproliferative effects of ZD1839 ('Iressa') on esophageal squamous carcinoma cells
134. Intermittent oral ZD1839 (Iressa), a novel epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), shows evidence of good tolerability and activity: Final results from phase I study
135. Final results of a phase I intermittent dose-escalation trial of ZD1839 ('Iressa') in Japanese patients with various solid tumors
136. Continuous administration of ZD1839 (Iressa), a novel oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in patients with five selected tumor types: Evidence of activity and good tolerability
137. A pilot trial demonstrates the safety of ZD1839 ('Iressa'), an oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), in combination with carboplatin (C) and paclitaxel (P) in previously untreated advanced non-small cell lung cancer (NSCLC)
138. Small molecule EGF receptor tyrosine kinase inhibitor ZD1839 (IRESSA) inhibits HER2/Neu (erb-2) overexpressing breast tumor cells
139. The EGFR-selective tyrosine kinase inhibitor ZD1839 ('Iressa') is an effective inhibitor of tamoxifen-resistant breast cancer growth
140. Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase
141. Inhibition of epidermal growth factor receptor-associated tyrosine phosphorylation in human carcinomas with CP-358,774: Dynamics of receptor inhibition in situ and antitumor effects in athymic mice
142. Inhibition of epidermal growth factor receptor (EGFR) by OSI-774, a specific EGFR inhibitor in malignant and normal tissues of cancer patients
143. Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies
144. Phase I dose escalation study of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor CP-358,774 in patients with advanced solid tumors
145. Dose and scheduleduration escalation of the epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor CP-358,774: A phase I and pharmacokinetic (PK) study
146. Dose-schedule-finding, pharmacokinetic (PK), biologic and functional imaging studies of OSI-774, a selective epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor
147. A phase II trial of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor OSI-774, following platinum-based chemotherapy, in patients (pts) with advanced, EGFR-expressing, non-small cell lung cancer (NSCLC)
148. Phase 2 evaluation of OSI-774, a potent oral antagonist of EGFR-TK in patients with advanced squamous cell carcinoma of the head and neck
149. Phase 2 evaluation of OSI-774, a potent oral antagonist of EGFR-TK in patients with advanced ovarian carcinoma
150. Proteasomes: Destruction as a programme
151. The ubiquitinproteasome pathway is required for processing the NFkappa B1 precursor protein and the activation of NF-kappa B
152. Proteasome inhibitors: A novel class of potent and effective antitumor agents
153. The proteasome inhibitor PS-341 in cancer therapy
154. Effect of proteasome inhibitor PS341 on cell cycle progression and cell cycle-related events: Implication for combination therapy with cell cycle dependent agents
155. Protease inhibitor-induced apoptosis: Accumulation of wt p53, p21WAF1/CIP1, and induction of apoptosis are independent markers of proteasome inhibition
156. A phase I trial of the proteasome inhibitor PS-341 in patients with advanced cancer
157. Novel proteasome inhibitor PS-341 inhibits activation of nuclear factor-kappaB, cell survival, tumor growth, and angiogenesis in squamous cell carcinoma
158. Dose-dependent inhibition of 20S proteasome results in serum 11-6 and PSA decline in patients (PTS) with androgen-independent prostate cancer (AIPCa) treated with the proteasome inhibitor PS-341
159. Preclinical effects of proteasome inhibitor PS-341 in combination chemotherapy for prostate cancer
160. Proteasome inhibition measurements: Clinical application
161. A phase I trial of the novel proteasome inhibitor PS341 in advanced solid tumor malignancies
162. PS-341: Phase I study of a novel proteasome inhibitor with pharmacodynamic endpoints
163. Clinical trials referral resource. Current clinical trials for the proteasome inhibitor PS-341
164. Histone acetylation and transcriptional regulatory mechanisms
165. Histone deacetylase: A regulator of transcription
166. Rb interacts with histone deacetylase to repress transcription
167. FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. III. Antitumor activities on experimental tumors in mice
168. P21-dependent g(1)arrest with downregulation of cyclin D1 and upregulation of cyclin E by the histone deacetylase inhibitor FR901228
169. Depsipeptide (FR901228): A novel therapeutic agent with selective, in vitro activity against human B-cell chronic lymphocytic leukemia cells
170. A phase I study of FR901228 (depsipeptide), a histone deacetylase inhibitor
171. Histone deacetylase inhibitor for the treatment of peripheral or cutaneous T-cell lymphoma
172. A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors
173. MS-275, a histone deacetylase inhibitor, selectively induces transforming growth factor beta type II receptor expression in human breast cancer cells
174. Inhibition of the association with nuclear matrix of pRB, p70 and p40 proteins along with the specific suppression of c-MYC expression by geldanamycin, an inhibitor of Src tyrosine kinase
175. Reversal of transformed phenotypes by herbimycin A in src oncogene expressed rat fibroblasts
176. Crystal structure of an Hsp90-geldanamycin complex: Targeting of a protein chaperone by an antitumor agent
177. Identification of a geldanamycin dimer that induces the selective degradation of HER-family tyrosine kinases
178. Geldanamycin as a potential anti-cancer agent: Its molecular target and biochemical activity
179. Phase I pharmacologic study of 17-(allylamino)-17-demethoxygeldanamycin (AAG) in adult patients with advanced solid tumors
180. Phase trial of 17-(allylamino)-17-Demethoxygeldanamycin (17-AAG) in patients (Pts) with advanced solid malignancies
181. Immunoconjugates of geldanamycin and anti-HER2 monoclonal antibodies: Antiproliferative activity on human breast carcinoma cell lines
182. A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells
183. 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway
184. 1 to S transition is mediated by effects on cyclin D1 mRNA and protein stability
185. 1 arrest in exponentially growing T-cell lines
186. Activity of rapamycin (AY-22,989) against transplanted tumors
187. CCI-779, a rapamycin analog and multifaceted inhibitor of signal transduction: A phase I study
188. CCI-779, a rapamycin analog with antitumor activity: A phase I study utilizing a weekly schedule
189. Changes in 18F-FDG uptake measured by PET as a pharmacodynamic end-point in anticancer therapy. How far have we got?