Li Yan, Xu Ziyi, Xie Tongji, Xing Puyuan, Ying Jianming, Li Junling
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Oncol. 2022 Aug 11;12:937282. doi: 10.3389/fonc.2022.937282. eCollection 2022.
mutations are the most important drivers of gene alterations in lung adenocarcinomas and are sensitive to -TKIs. However, resistance to -TKIs is inevitable in the majority of -mutated lung cancer patients. Numerous resistant mechanisms have been revealed to date, and more are still under investigation. Owing to the selective pressure, intratumoral heterogeneity may exist after resistance, especially in patients after multiple lines of treatment. For those patients, it is important to choose therapies focused on the trunk/major clone of the tumor in order to achieve optimal clinical benefit. Here, we will report an -mutated lung adenocarcinoma patient with heterogeneity of resistant mechanisms including amplification, large fragment deletion of , and histological transformations after targeted treatments. In our case, amplification seemed to be the major clone of the resistant mechanism according to the next-generation sequencing (NGS) results of both liquid biopsy monitoring and tissue biopsies. In consideration of the high amplification level, the patient was administered by combination treatment with -TKI plus nimotuzumab, an anti- monoclonal antibody (mAb), and achieved a certain degree of clinical benefit. Our case sheds light on the treatment of -mutant patients with amplification and indicates that a combination of -TKI with anti- mAb might be one of the possible treatment options based on genetic tests. Moreover, the decision on therapeutic approaches should focus on the major clone of the tumor and should make timely adjustments according to the dynamic changes of genetic characteristics during treatment.
突变是肺腺癌基因改变的最重要驱动因素，并且对-TKIs敏感。然而，在大多数-mutated肺癌患者中，对-TKIs产生耐药是不可避免的。迄今为止，已经揭示了许多耐药机制，并且仍有更多机制正在研究中。由于选择性压力，耐药后肿瘤内可能存在异质性，尤其是在接受多线治疗的患者中。对于这些患者，选择针对肿瘤主干/主要克隆的治疗方法以获得最佳临床获益非常重要。在此，我们将报告一例-mutated肺腺癌患者，其耐药机制存在异质性，包括扩增、大片段缺失以及靶向治疗后的组织学转化。在我们的病例中，根据液体活检监测和组织活检的下一代测序（NGS）结果，扩增似乎是耐药机制的主要克隆。考虑到高扩增水平，该患者接受了-TKI联合抗单克隆抗体（mAb）尼妥珠单抗的联合治疗，并取得了一定程度的临床获益。我们的病例为扩增的-mutant患者的治疗提供了启示，并表明-TKI与抗mAb联合可能是基于基因检测的一种可能治疗选择。此外，治疗方法的决策应聚焦于肿瘤的主要克隆，并应根据治疗期间基因特征的动态变化及时调整。
