Sequencing PEComas: Viewing Unicorns through the Molecular Looking Glass.
Sequencing PEComas: Viewing Unicorns through the Molecular Looking Glass.
复制标题
PEComas 测序：通过分子镜子观察独角兽。
DOI：
10.1159/000510650
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发表时间：
2021
期刊：
影响因子：
3.5
通讯作者：
Subbiah,Vivek
中科院分区：
文献类型：
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作者：
Groisberg,Roman;Subbiah,Vivek
三年前，在一篇关于下一代测序（NGS）在肉瘤中的作用的评论中，我们写道，“精确肿瘤学”迄今为止仅限于少数肉瘤病例报告[1]。在很短的时间内，我们见证了在肉瘤中使用NGS的病例的爆炸性增长。随着NTRK抑制剂（larotrectinib，entrectinib）在NTRK阳性实体瘤（其中许多是肉瘤）中的组织不可知性批准，pembrolizumab在微卫星不稳定性高/错配修复缺陷（MSI-H/dMMR）癌症和转移性肿瘤突变负荷高（TMB-H≥ 10个突变/兆碱基）癌症中的批准，NGS正在成为肉瘤的标准治疗。此外，NGS还完善了关于胃肠道间质瘤（GIST）辅助治疗的讨论[2]，确定了血管瘤免疫治疗的预测性生物标志物[3]，并与INI-1基因缺失/SMARCB 1缺陷型上皮样肉瘤靶向治疗的出现更加相关[4]。从研究到实践，NGS正在成为我们在区分和征服肉瘤的战争中最有力的武器[5]。“PEComa”是一种罕见的软组织肉瘤亚型，起源于血管周围的上皮样细胞，因此称为PEComa。恶性PEComas（mPEComas）是一种罕见的疾病亚型，突出表现为侵袭性局部和远处复发。这种恶性变异体治疗的最新突破来自AMPECT试验，该试验评估了nab-西罗莫司（纳米颗粒白蛋白结合西罗莫司，一种mTOR抑制剂），显示缓解率为39%（95%CI：22-58%）。中位无进展生存期为8.9个月（95%CI：5.5-未达到），1年总生存率为89%[6]。在TSC 2突变患者亚组的探索性分析中，独立审查的缓解率为89%（95% CI：57-99%）。
Three years ago, in a review on the role of next-generation sequencing (NGS) in sarcomas, we wrote that “precision oncology” has so far been limited to few case reports in sarcomas [1]. In just a short time, we have witnessed an explosionin the use of cases justifying NGS in sarcomas. With the tissue-agnostic approval of NTRK inhibitors (larotrectinib, entrectinib) in NTRK-positive solid tumors (many of them sarcomas), pembrolizumab in microsatellite instability high/deficient mismatch repair (MSI-H/dMMR) cancers and metastatic tumor mutational burden-high (TMB-H≥ 10 mutations/megabase) cancers, NGS is becoming the standard of care in sarcomas. In addition, NGS has refined the discussion on adjuvant therapy in gastrointestinal stromal tumors (GIST)[2], identified predictive biomarkers to immunotherapy in angiosarcomas [3], and become ever more relevant with the emergence of targeted therapies in INI-1 gene loss/SMARCB1-deficient epithelioid sarcomas [4]. From research to practice, NGS is becoming our most powerful weapon in the war to divide and conquer sarcomas [5].“PEComas” are a rare subtype of soft-tissue sarcoma arising from the perivascular epithelioid cell, hence PEComa. Malignant PEComas (mPEComas) are a rare subtype of the disease, highlighted by aggressive local and distant recurrences. A recent breakthrough in the treatment of this malignant variant came from the AMPECT trial, which evaluated nab-sirolimus (nano-particle albumin-bound sirolimus, an mTOR inhibitor) and showed a response rate of 39%(95% CI: 22–58%). The median progression-free survival was 8.9 months (95% CI: 5.5–not reached) and the 1-year overall survival rate was 89%[6]. In an exploratory analysis of the subset of patients with TSC2 mutations, the independently reviewed response rate was 89%(95% CI: 57–99%).