TMPRSS2:ERG Gene Fusion Might Predict Resistance to PARP Inhibitors in Metastatic Castration-resistant Prostate Cancer.

IF 1.6 4区医学 Q4 ONCOLOGY Anticancer research Pub Date : 2024-10-01 DOI:10.21873/anticanres.17250

Tim Svenstrup Poulsen, Anders Nygaard Lørup, Per Kongsted, Rikke Løvendahl Eefsen, Martin Højgaard, Estrid Vilma Høgdall

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Abstract

Background/aim: The emergence of novel DNA damage repair (DDR) pathways in molecular-target therapy drugs (MTTD) has shown promising outcomes in treating patients with metastatic castration-resistant prostate cancer (mCRPC). About 25% of mCRPC patients have actionable deleterious aberrations in DDR genes, primarily in the homologous recombination (HR) pathway. However, the response rate in patients with BRCA1/2 or mutations in HRR-related genes is only 45%-55%, when exposed to poly ADP ribose polymerase (PARP) inhibitor-based therapy (PARPi). A frequent characteristic feature of prostate cancer (PC) is the occurrence of genomic rearrangement that affects the transmembrane protease serine 2 (TMPRSS2) and E26 transformation-specific (ETS)- transcription factor-related gene (ERG).

Materials and methods: In this study, a total of 114 patients with mCRPC had their RNA and DNA sequenced using next-generation sequencing.

Results: Based on their genetic profile of deleterious gene alterations of BRCA1/2 or ATM, six patients were selected for PARPi. Patients with TMPRSS2:ERG gene fusion and homozygous alteration in ATM or BRCA2 (n=2) or heterozygous alterations (BRCA1 or BRCA2) and lack of TMPRSS2:ERG gene fusion (n=2) did not show clinical benefit from PARPi (treatment duration <16 weeks). In contrast, patients (n=2) without TMPRSS2:ERG gene fusion and homozygous deleterious alterations in ATM or BRCA2 all had clinical benefit from PARPi (treatment duration ≥16 weeks).

Conclusion: The TMPRSS2:ERG transcript product might be used as a PARPi resistance biomarker.

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TMPRSS2:ERG基因融合可预测转移性阉割抗性前列腺癌对PARP抑制剂的耐药性

背景/目的：分子靶向治疗药物（MTTD）中出现的新型DNA损伤修复（DDR）通路在治疗转移性耐阉割前列腺癌（mCRPC）患者方面取得了可喜的成果。约 25% 的 mCRPC 患者的 DDR 基因存在可操作的有害畸变，主要是在同源重组 (HR) 途径中。然而，当接受基于聚 ADP 核糖聚合酶（PARP）抑制剂的治疗（PARPi）时，BRCA1/2 或 HRR 相关基因突变患者的应答率仅为 45%-55%。前列腺癌（PC）的一个常见特征是发生影响跨膜丝氨酸蛋白酶2（TMPRSS2）和E26转化特异性（ETS）转录因子相关基因（ERG）的基因组重排：本研究共对114名mCRPC患者的RNA和DNA进行了新一代测序：结果：根据BRCA1/2或ATM有害基因改变的遗传特征，6名患者被选中接受PARPi治疗。TMPRSS2:ERG转录产物可用作PARPi耐药性生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

期刊介绍： ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.