伴有致病性体细胞BRCA1突变的晚期卵巢癌患者在一线铂类化疗后对PARP抑制剂的耐药性

IF 1.8 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics & Personalized Medicine Pub Date : 2023-01-01 DOI:10.2147/PGPM.S397827
Lan Zhong, Rutie Yin, Liang Song
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摘要

PARP抑制剂(PARPi)是伴有生殖系和致病性BRCA1/2体细胞突变的晚期上皮性卵巢癌(EOC)患者一线铂类化疗后的维持治疗。然而,与化疗一样,患者可能对PARPi产生耐药性。异质体细胞BRCA突变产生的选择压力可能导致化疗或PARPi耐药肿瘤。在这里,我们提出了一个病例,患者携带致病性p.Glu143* (c.427G>T)体细胞BRCA1突变,在细胞减少手术和铂基化疗后对奥拉帕尼产生耐药性。我们要求进行血浆ctDNA分析(复发病变的组织活检由于其解剖位置是禁忌的),以找出可能的耐药机制。ctDNA分析未检测到之前发现的致病性体细胞BRCA1 p.g u143* (c.427G>T)突变。携带致病性BRCA1突变的肿瘤细胞可能被铂类化疗消除,只留下没有BRCA突变的肿瘤细胞增殖。
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Resistance to PARP Inhibitors After First-Line Platinum-Based Chemotherapy in a Patient with Advanced Ovarian Cancer with a Pathogenic Somatic BRCA1 Mutation.

PARP inhibitors (PARPi) are the maintenance therapy after first line platinum-based chemotherapy for patients with advanced epithelial ovarian cancer (EOC) with germline and pathogenic somatic BRCA1/2 mutations. However, as with chemotherapy, patients can develop resistance to PARPi. The selective pressure generated by heterogeneous somatic BRCA mutations may give rise to chemotherapy or PARPi resistant tumors. Here, we present the case of a patient harboring a pathogenic p.Glu143* (c.427G>T) somatic BRCA1 mutation conferring resistance to olaparib following cytoreductive surgery and platinum-based chemotherapy. We ordered a plasma ctDNA analysis (tissue biopsy of recurrent lesions was contraindicated due to their anatomical location) to figure out the possible resistance mechanism. Analysis of ctDNA did not detect the pathogenic somatic BRCA1 p.Glu143* (c.427G>T) mutation seen before. The tumor cells harboring the pathogenic BRCA1 mutation were probably eliminated by the platinum-based chemotherapy, leaving only those without BRCA mutations to proliferate.

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来源期刊
Pharmacogenomics & Personalized Medicine
Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
3.30
自引率
5.30%
发文量
110
审稿时长
16 weeks
期刊介绍: Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.
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