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International Journal of Molecular Sciences

International Journal of Molecular Sciences

IF: 4.9
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Dual Inhibition of EGFR and IGF-1R Signaling Leads to Enhanced Antitumor Efficacy against Esophageal Squamous Cancer

Published:8 September 2022 DOI: 10.3390/ijms231810382 PMID: 36142299
Jia Kang, Zanzan Guo, Haoqi Zhang, Rongqi Guo, Xiaofei Zhu, Xiaofang Guo

Abstract

Both the epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF-1R) have been implicated in the development of cancers, and the increased expression of both receptors has been observed in esophageal cancer. However, the tyrosine kinase inhibitors of both receptors have thus far failed to provide clinical benefits for esophageal cancer patients. Studies have confirmed the complicated crosstalks that exist between the EGFR and IGF-1R pathways. The EGFR and IGF-1R signals act as mutual compensation pathways, thereby conveying resistance to EGFR or IGF-1R inhibitors when used alone. This study evaluated the antitumor efficacy of the EGFR/HER2 inhibitors, gefitinib and lapatinib, in combination with the IGF-1R inhibitor, linsitinib, on the esophageal squamous cell carcinoma (ESCC). Gefitinib or lapatinib, in combination with linsitinib, synergistically inhibited the proliferation, migration, and invasion of ESCC cells, caused significant cell cycle arrest, and induced marked cell apoptosis. Their combination demonstrated stronger inhibition on the activation of EGFR, HER2, and IGF-1R as well as the downstream signaling molecules. In vivo, the addition of linsitinib to gefitinib or lapatinib also potentiated the inhibition effects on the growth of xenografts. Our results suggest the next clinical exploration of the combination of gefitinib or lapatinib with linsitinib in the treatment of ESCC patients.

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Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
Gefitinib 184475-35-2 C22H24ClFN4O3 818 suppliers $5.00-$1191.00
Gefitinib 184475-35-2 C22H24ClFN4O3 818 suppliers $5.00-$1191.00
Gefitinib 184475-35-2 C22H24ClFN4O3 818 suppliers $5.00-$1191.00
Gefitinib 184475-35-2 C22H24ClFN4O3 818 suppliers $5.00-$1191.00
Lapatinib 231277-92-2 C29H26ClFN4O4S 572 suppliers $10.00-$1900.00
Lapatinib 231277-92-2 C29H26ClFN4O4S 572 suppliers $10.00-$1900.00
Lapatinib 231277-92-2 C29H26ClFN4O4S 572 suppliers $10.00-$1900.00
Lapatinib 231277-92-2 C29H26ClFN4O4S 572 suppliers $10.00-$1900.00
Linsitinib 867160-71-2 C26H23N5O 191 suppliers $16.00-$4173.50
Linsitinib 867160-71-2 C26H23N5O 191 suppliers $16.00-$4173.50
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