scholarly journals Discovery of a Highly Potent and Broadly Effective Epidermal Growth Factor Receptor and HER2 Exon 20 Insertion Mutant Inhibitor

2018 ◽  
Vol 57 (36) ◽  
pp. 11629-11633 ◽  
Author(s):  
Jaebong Jang ◽  
Jieun Son ◽  
Eunyoung Park ◽  
Takayuki Kosaka ◽  
Jamie A. Saxon ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Insertion Mutant ◽  
Epidermal Growth ◽  
Exon 20

scholarly journals Discovery of a Highly Potent and Broadly Effective Epidermal Growth Factor Receptor and HER2 Exon 20 Insertion Mutant Inhibitor

2018 ◽  
Vol 130 (36) ◽  
pp. 11803-11807
Author(s):  
Jaebong Jang ◽  
Jieun Son ◽  
Eunyoung Park ◽  
Takayuki Kosaka ◽  
Jamie A. Saxon ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Insertion Mutant ◽  
Epidermal Growth ◽  
Exon 20

Positive progress for non-small cell lung cancer with epidermal growth factor receptor exon 20 insertion mutations: A novel targeted therapy option

2021 ◽  
pp. 107815522110449
Author(s):  
Weisan Zhang ◽  
Xifeng Dong
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Receptor Gene ◽  
Growth Factor Receptor ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Exon 20 ◽  
Insertion Mutations ◽  
Gene Exon

Epidermal growth factor receptor gene exon 20 insertion mutations are seen in ∼4–12% of patients with epidermal growth factor receptor-mutant non-small cell lung cancer. However, there is no targeted therapy approved for the treatment of non-small cell lung cancer patients with these rare epidermal growth factor receptor mutations. Previous studies revealed that epidermal growth factor receptor gene exon 20 insertion mutations are unique in their ability to activate epidermal growth factor receptor without the typical structural changes associated with the common epidermal growth factor receptor mutations, reducing the clinical efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors currently approved for non-small cell lung cancer. Therefore, there is an urgent need to identify active epidermal growth factor receptor-tyrosine kinase inhibitors and other effective treatment strategies for non-small cell lung cancer patients with epidermal growth factor receptor gene exon 20 insertion mutations. Mobocertinib is a novel irreversible epidermal growth factor receptor-tyrosine kinase inhibitor that selectively targets epidermal growth factor receptor gene exon 20 insertion mutations. Preclinical study revealed that mobocertinib inhibited the viability of epidermal growth factor receptor gene exon 20 insertion mutations-driven patient-derived xenografts and murine orthotopic tumors more potently than traditional epidermal growth factor receptor-tyrosine kinase inhibitors. In a study recently published in Cancer Discovery, Gonzalvez et al. assessed the safety, tolerability, and antitumor efficacy of mobocertinib in metastatic non-small cell lung cancer patients with epidermal growth factor receptor gene exon 20 insertion mutations. They found that non-small cell lung cancer patients with epidermal growth factor receptor gene exon 20 insertion mutations can benefit from mobocertinib treatment. Additionally, the treatment-related toxicity of mobocertinib was manageable. These findings lay the foundation for the application of mobocertinib in epidermal growth factor receptor gene exon 20 insertion-mutated non-small cell lung cancer.

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