Minami Seigo, Ihara Shouichi, Tanaka Tsunehiro, Okada Hideyasu, Hashimoto Kazuki, Komuta Kiyoshi
Department of Respiratory Medicine, Osaka Police Hospital, Osaka, Japan.
Case Rep Oncol. 2019 Feb 20;12(1):178-182. doi: 10.1159/000497316. eCollection 2019 Jan-Apr.
Uncommon epidermal growth factor receptor (EGFR) gene mutations include G719S, T790M and S768I. T790M gatekeeper mutation is the most frequent mechanism of acquired drug resistance to first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs). Osimertinib is a specific EGFR-TKI to overcome T790M resistance mutation. However, owing to a new drug and a rare mutation type, it remains unknown whether osimertinib is effective for acquired S768I. Herein, we reported a 76 year-old woman with pulmonary adenocarcinoma, which had acquired EGFR mutations of S768I and T790M in addition to original G719S after long gefitinib treatment. These mutations were detected in biopsy specimen of liver metastases. During two months of osimertinib, multiple liver metastases progressively enlarged. This case suggested that acquired S768I mutation might be resistant to osimeritinib, despite of co-occurrence of T790M.
罕见的表皮生长因子受体（EGFR）基因突变包括G719S、T790M和S768I。T790M守门基因突变是第一代和第二代EGFR酪氨酸激酶抑制剂（TKIs）获得性耐药的最常见机制。奥希替尼是一种克服T790M耐药突变的特异性EGFR-TKI。然而，由于这是一种新药且突变类型罕见，奥希替尼对获得性S768I是否有效仍不清楚。在此，我们报告了一名76岁的肺腺癌女性患者，在长期使用吉非替尼治疗后，除了原有的G719S外，还获得了S768I和T790M的EGFR突变。这些突变在肝转移灶的活检标本中被检测到。在使用奥希替尼的两个月期间，多个肝转移灶逐渐增大。该病例表明，尽管同时存在T790M，但获得性S768I突变可能对奥希替尼耐药。
