Chen Zhujun, Wang Kang, Zhao Lintao, Gong Liang
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Army Medical University, Chongqing, China.
Front Oncol. 2023 May 16;13:1190100. doi: 10.3389/fonc.2023.1190100. eCollection 2023.
Mutations in the human breast cancer susceptibility gene 2 (breast cancer 2, BRCA2) increase the risk of breast, ovarian and other cancers. Olaparib, an oral poly[adenosine diphosphate (ADP)-ribose] polymerase (PARP) inhibitor, is usually prescribed to treat BRCA mutated tumors, especially breast and ovarian cancers. Programmed cell death-1 (PD-1) inhibitors have revolutionized the treatment of lung cancer and many other cancers by destroying the interaction between receptors with ligands in the tumor-immune microenvironment and enabling T cells to recognize and attack cancer cells.
In our study, we report a patient with advanced BRCA2 lung squamous cell carcinoma who received platinum-based chemotherapy combined with paclitaxel. Seven months later, the disease progressed. BRCA2 mutations were detected in peripheral blood by next-generation sequencing. After 2 months of treatment with Olaparib combined with Cindilimab, the patient was in partial remission and the progression-free survival (PFS) lasted for 6 months, but the patient developed immune renal damage.
This study adds to the clinical data for the treatment of BRCA2 mutant non-small cell lung cancer by demonstrating that lung squamous cell carcinoma has a good response to PARP inhibitors. It also serves as a reminder that there may still be some negative effects from targeted superimposed immunotherapy.
人类乳腺癌易感基因2(乳腺癌2,BRCA2)的突变会增加患乳腺癌、卵巢癌和其他癌症的风险。奥拉帕利是一种口服聚[腺苷二磷酸(ADP)-核糖]聚合酶(PARP)抑制剂,通常用于治疗BRCA突变的肿瘤,尤其是乳腺癌和卵巢癌。程序性细胞死亡蛋白1(PD-1)抑制剂通过破坏肿瘤免疫微环境中受体与配体之间的相互作用,使T细胞能够识别并攻击癌细胞,从而彻底改变了肺癌和许多其他癌症的治疗方式。
在我们的研究中,我们报告了一名晚期BRCA2肺鳞状细胞癌患者,该患者接受了铂类化疗联合紫杉醇治疗。七个月后,疾病进展。通过下一代测序在外周血中检测到BRCA2突变。在使用奥拉帕利联合信迪利单抗治疗2个月后,患者部分缓解,无进展生存期(PFS)持续了6个月,但患者出现了免疫性肾损伤。
本研究通过证明肺鳞状细胞癌对PARP抑制剂有良好反应,增加了BRCA2突变型非小细胞肺癌治疗的临床数据。它还提醒人们,靶向叠加免疫治疗可能仍然存在一些负面影响。