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奥拉帕利联合PD-1抑制剂治疗晚期肺鳞状细胞癌中的BRCA2突变:一例报告

BRCA2 mutation in advanced lung squamous cell carcinoma treated with Olaparib and a PD-1 inhibitor: a case report.

作者信息

Chen Zhujun, Wang Kang, Zhao Lintao, Gong Liang

机构信息

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Army Medical University, Chongqing, China.

出版信息

Front Oncol. 2023 May 16;13:1190100. doi: 10.3389/fonc.2023.1190100. eCollection 2023.

Abstract

BACKGROUND

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.

CASE DESCRIPTION

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.

CONCLUSIONS

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.

摘要

背景

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。

病例描述

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。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7158/10228719/6ae024b384ce/fonc-13-1190100-g001.jpg

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