A phase II trial of neoadjuvant erlotinib in patients with muscle‐invasive bladder cancer undergoing radical cystectomy: clinical and pathological results

Pruthi, Raj S.; Nielsen, Matthew E.; Heathcote, Samuel A; Wallen, Eric; Rathmell, W. Kim; Godley, Paul A.; Whang, Young E.; Schultz, Heather; Grigson, Gayle; Smith, Angela; Kim, William

doi:10.1111/j.1464-410x.2009.09101.x

Cited by 104 publications

(65 citation statements)

References 24 publications

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“…Initial studies showed great promise for the use of EGFR inhibitors in the setting of advanced bladder cancer in humans (31,32). As expected, Iressa treatment strikingly decreased levels of phosphorylated EGFR, AKT, and extracellular signal-regulated kinase (ERK; data not shown.).…”

Section: Discussionsupporting

confidence: 52%

Modulation of Gene Expression and Cell-Cycle Signaling Pathways by the EGFR Inhibitor Gefitinib (Iressa) in Rat Urinary Bladder Cancer

Lü

Liu

Bergh

et al. 2012

Cancer Prevention Research

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The epidermal growth factor receptor inhibitor Iressa has shown strong preventive efficacy in the N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) model of bladder cancer in the rat. To explore its antitumor mechanism, we implemented a systems biology approach to characterize gene expression and signaling pathways in rat urinary bladder cancers treated with Iressa. Eleven bladder tumors from control rats, seven tumors from rats treated with Iressa, and seven normal bladder epithelia were profiled by the Affymetrix Rat Exon 1.0 ST Arrays. We identified 713 downregulated and 641 upregulated genes in comparing bladder tumors versus normal bladder epithelia. In addition, 178 genes were downregulated and 96 genes were upregulated when comparing control tumors versus Iressa-treated tumors. Two coexpression modules that were significantly correlated with tumor status and treatment status were identified [r ¼ 0.70, P ¼ 2.80 Â 10 À15 (bladder tumor vs. normal bladder epithelium) and r ¼ 0.63, P ¼ 2.00 Â 10 À42 (Iressa-treated tumor vs. control tumor), respectively]. Both tumor module and treatment module were enriched for genes involved in cell-cycle processes. Twenty-four and twenty-one highly connected hub genes likely to be key drivers in cell cycle were identified in the tumor module and treatment module, respectively. Analysis of microRNA genes on the array chips showed that tumor module and treatment module were significantly associated with expression levels of let-7c (r ¼ 0.54, P ¼ 3.70 Â 10 À8 and r ¼ 0.73, P ¼ 1.50 Â 10 À65 , respectively). These results suggest that let-7c downregulation and its regulated cell-cycle pathway may play an integral role in governing bladder tumor suppression or collaborative oncogenesis and that Iressa exhibits its preventive efficacy on bladder tumorigenesis by upregulating let-7 and inhibiting the cell cycle. Cell culture study confirmed that the increased expression of let-7c decreases Iressa-treated bladder tumor cell growth. The identified hub genes may also serve as pharmacodynamic or efficacy biomarkers in clinical trials of chemoprevention in human bladder cancer. Cancer Prev Res; 5(2); 248-59. Ó2011 AACR.

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Section: Discussionsupporting

confidence: 52%

Modulation of Gene Expression and Cell-Cycle Signaling Pathways by the EGFR Inhibitor Gefitinib (Iressa) in Rat Urinary Bladder Cancer

Lü

Liu

Bergh

et al. 2012

Cancer Prevention Research

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“…At a mean follow-up of 24.8 months, 50% of the patients were alive and still disease-free. This suggests that EGFR inhibition could be beneficial for some patients with mUC but that, for reasons still not understood, resistance to EGFR inhibitors could develop after or in conjunction with chemotherapy [79].…”

Section: Egfr Inhibitorsmentioning

confidence: 99%

Molecular biology and targeted therapies for urothelial carcinoma

Seront

Machiels

2015

Cancer Treatment Reviews

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“…A phase II study evaluated the clinicopathologic efficacy of erlotinib in patients with stage T2 disease [40]. In this study 20 patients received neoadjuvant erlotinib.…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Targeting the Epidermal Growth Factor Receptor in Bladder Cancer

Weintraub¹

2013

J Carcinogene Mutagene

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A phase II trial of neoadjuvant erlotinib in patients with muscle‐invasive bladder cancer undergoing radical cystectomy: clinical and pathological results

Cited by 104 publications

References 24 publications

Modulation of Gene Expression and Cell-Cycle Signaling Pathways by the EGFR Inhibitor Gefitinib (Iressa) in Rat Urinary Bladder Cancer

Modulation of Gene Expression and Cell-Cycle Signaling Pathways by the EGFR Inhibitor Gefitinib (Iressa) in Rat Urinary Bladder Cancer

Molecular biology and targeted therapies for urothelial carcinoma

Targeting the Epidermal Growth Factor Receptor in Bladder Cancer

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