Targeted epidermal growth factor receptor therapy in malignant pleural mesothelioma: Where do we stand?

2011 ◽  
Vol 37 (7) ◽  
pp. 533-542 ◽  
Author(s):  
Vijay Agarwal ◽  
Michael J. Lind ◽  
Lynn Cawkwell
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Malignant Pleural Mesothelioma ◽  
Growth Factor Receptor ◽  
Pleural Mesothelioma ◽  
Epidermal Growth

scholarly journals Biodistribution and Tumor Uptake of 67Ga-Nimotuzumab in a Malignant Pleural Mesothelioma Xenograft

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3138 ◽  
Author(s):  
Vanessa Izquierdo-Sánchez ◽  
Saé Muñiz-Hernández ◽  
Héctor Vázquez-Becerra ◽  
Judith Pacheco-Yepez ◽  
Mario Romero-Piña ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Malignant Pleural Mesothelioma ◽  
Growth Factor Receptor ◽  
In Vivo Studies ◽  
Pleural Mesothelioma ◽  
Tumor Uptake ◽  
Epidermal Growth ◽  
Significant Uptake

Malignant pleural mesothelioma (MPM) is the most common tumor of the pulmonary pleura. It is a rare and aggressive malignancy, generally associated with continuous occupational exposure to asbestos. Only a multimodal-approach to treatment, based on surgical resection, chemotherapy and/or radiation, has shown some benefits. However, the survival rate remains low. Nimotuzumab (h-R3), an anti-EGFR (epidermal growth factor receptor) humanized antibody, is proposed as a promising agent for the treatment of MPM. The aim of this research was to implement a procedure for nimotuzumab radiolabeling to evaluate its biodistribution and affinity for EGF (epidermal growth factor) receptors present in a mesothelioma xenograft. Nimotuzumab was radiolabeled with 67Ga; radiolabel efficiency, radiochemical purity, serum stability, and biodistribution were evaluated. Biodistribution and tumor uptake imaging studies by microSPECT/CT in mesothelioma xenografts revealed constant nimotuzumab uptake at the tumor site during the first 48 h after drug administration. In vivo studies using MPM xenografts showed a significant uptake of this radioimmunoconjugate, which illustrates its potential as a biomarker that could promote its theranostic use in patients with MPM.

Phase II Study of Erlotinib in Patients With Malignant Pleural Mesothelioma: A Southwest Oncology Group Study

2007 ◽  
Vol 25 (17) ◽  
pp. 2406-2413 ◽  
Author(s):  
Linda L. Garland ◽  
Cathryn Rankin ◽  
David R. Gandara ◽  
Saul E. Rivkin ◽  
Katherine M. Scott ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Survival Time ◽  
Growth Factor Receptor ◽  
Pleural Mesothelioma ◽  
Phosphatidylinositol 3 Kinase ◽  
Epidermal Growth ◽  
Egfr Tki ◽  
Phosphatidylinositol 3

Purpose Malignant pleural mesothelioma (MPM) expresses high levels of epidermal growth factor receptor (EGFR), and preclinical studies have identified antitumor activity of EGFR tyrosine kinase inhibitors (TKIs) in MPM. We conducted a phase II trial of the EGFR TKI erlotinib in previously untreated patients with MPM. Patients and Methods Patients with measurable and nonmeasurable disease were treated with erlotinib 150 mg/d on days 1 through 28 of each 28-day dosing cycle. Archived patient tumors were analyzed for immunohistochemical expression of EGFR, phospho-EGFR, human epidermal growth factor receptor 2 (HER2), phospho–extracellular signal-regulated kinase (ERK), and phosphatase and tensin homolog (PTEN) and phosphorylation of members of the phosphatidylinositol 3-kinase/Akt signaling pathway. Results Sixty-three patients were treated on the study. EGFR was highly expressed in 75% of patient tumors, as was phospho-ERK (82%), phospho-Akt (84%), phospho–mammalian target of rapamycin (74%), and phospho-forkhead (74%). HER2 was rarely expressed, and loss of PTEN was rare. For 33 patients with measurable disease, there were no objective responses; 14 patients (42%) had stable disease, 15 patients (45%) had disease progression, and four patients had inadequate assessments to determine response. Toxicities were mainly constitutional (51%), dermatologic (82%), and GI (52%); there was one death on trial, which was related to dyspnea. Median overall survival time was 10 months; 1-year survival rate was 43%; and median progression-free survival time was 2 months. Conclusion Single-agent erlotinib was not effective in MPM, despite high expression of EGFR. Activation of the ERK and phosphatidylinositol 3-kinase/Akt downstream pathways are possible resistance mechanisms to EGFR TKI. The activated phosphatidylinositol 3-kinase/Akt pathway is a potential therapeutic target for MPM.

scholarly journals A comparison of epidermal growth factor receptor expression in malignant peritoneal and pleural mesothelioma

2012 ◽  
Vol 62 (4) ◽  
pp. 226-231 ◽  
Author(s):  
Yasunori Enomoto ◽  
Takahiko Kasai ◽  
Maiko Takeda ◽  
Masato Takano ◽  
Kouhei Morita ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Pleural Mesothelioma ◽  
Epidermal Growth
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