Proto-oncogene定向靶向治疗在老年多发性原发肿瘤患者中的效益有限。一名ALK阳性肺腺癌患者通过3年的crizotinib靶向治疗后出现获得性耐药。意外发现胆囊原发肿瘤。治疗时使用了Lenvatinib。同时，通过比较肿瘤驱动变异基因的生物信息学方法，分析了crizotinib治疗前后的下一代测序结果。患者死于腹水和肝功能衰竭。此外，旁路激活是该患者获得性耐药的主要原因，肿瘤抑制基因和衰老相关基因的异常表达可能是第二个原发肿瘤的原因之一。老年肿瘤学患者的前后治疗序列比较具有研究价值。对于诊断，精准的生物信息学分析和再次活检同等重要。对于治疗，对于衰老相关情况，需要进行潜在的治疗，例如p53基因替代治疗和CAR-T治疗。Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.

Proto-oncogene-oriented targeted therapy has limited benefits in elderly patients with multiple primary tumors.A woman with anaplastic lymphoma kinase-positive lung adenocarcinoma developed acquired resistance after 3 years of targeted therapy with crizotinib.Diagnosis of unexpected subsequent primary gallbladder tumor.Lenvatinib was administered therapeutically. Meanwhile, next-generation sequencing results before and after crizotinib treatment were analyzed by comparing the tumor-driving mutation genes with bioinformatics methods.The patient died of ascites and liver failure. Furthermore, bypass activation was found to be the main reason for acquired drug resistance for this patient, and the abnormal expression of tumor suppressor genes and senescence-related genes was the likely cause of the second primary tumor.A bioinformatic comparison of pre- and post-treatment sequencing in elderly oncology patients is of interest.For diagnosing, precision bioinformatics analysis and repeat biopsy are equally valuable. For therapy, potential therapy such as p53 gene replacement therapy and CAR-T therapy need to be practiced for senescence-related conditions.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.