Absence of common activating mutations of the epidermal growth factor receptor gene in thyroid cancers from American and Japanese patients

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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Epidermal growth factor receptor gene mutations in papillary thyroid carcinoma

International Journal of Cancer ◽

10.1002/ijc.24250 ◽

2008 ◽

Vol 124 (11) ◽

pp. 2744-2749 ◽

Cited By ~ 34

Author(s):

Katsuhiro Masago ◽

Ryo Asato ◽

Shiro Fujita ◽

Shigeru Hirano ◽

Yoshihiro Tamura ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Papillary Thyroid Carcinoma ◽

Epidermal Growth Factor ◽

Thyroid Carcinoma ◽

Receptor Gene ◽

Growth Factor Receptor ◽

Gene Mutations ◽

Papillary Thyroid ◽

Epidermal Growth

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Frequency of EGFR Mutation and EML4-ALK fusion gene in Arab Patients with Adenocarcinoma of the Lung

Forum of Clinical Oncology ◽

10.1515/fco-2015-0009 ◽

2015 ◽

Vol 6 (2) ◽

pp. 19-23

Author(s):

Hanan Ezzat Shafik ◽

Mohamed Ashour

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Egfr Mutation ◽

Fusion Gene ◽

Receptor Gene ◽

Growth Factor Receptor ◽

Egfr Mutations ◽

Anaplastic Lymphoma ◽

Epidermal Growth

Abstract Introduction: Improvement in the clinical outcome of lung cancer is likely to be achieved by identification of the molecular events that underlie its pathogenesis. The frequency of epidermal growth factor receptor (EGFR) mutations is ethnicity-dependent, with a higher proportion in Asian populations than in whites, while the incidence of EML4-ALK (echinoderm microtubule-associated-protein like 4-anaplastic lymphoma kinase) fusion gene ranged from 1.6% to 16.4% in patients with NSCLC and these individuals were distinct from those harbouring mutations in the epidermal growth factor receptor gene. This study was conducted to determine the frequency of EGFR mutation and EML4-ALK fusion gene in our population and to determine the effect of different clinicopathological features on the expression of those mutations in patients with lung adenocarcinoma. Results: EGFR mutations were detected in approximately 33% of our patients in this series; the most frequently detected mutation was exon 19 deletion. EML4-ALK fusion gene was detected in 7.3% of patients. Conclusion: Our population exhibited the incidence of EGFR mutation approximately similar to that reported in East Asia and Japanese patients, higher than that recorded in USA, and Australia. However, more studies with larger patients’ numbers are needed to verify this finding.

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