【佳学基因靶向药物基因检测】携带 BRAFV600E 突变的甲状腺乳头状癌类器官揭示了基于 BRAF 抑制剂的联合疗法的潜在有益作用

基因治疗肿瘤方法贼新简介

研讨三甲医师职称提升肿瘤学在《肿瘤诊断基因与转移分析》收录《J Transl Med》在 2023 Jan 9;21(1):9.发表了一篇题目为《》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Dong Chen, Xi Su, Lizhang Zhu, Hao Jia, Bin Han, Haibo Chen, Qingzhuang Liang, Chenchen Hu, Hao Yang, Lisa Liu, Peng Li, Wei Wei, Yongsheng Zhao等完成。促进了肿瘤的正确治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤基因检测及靶向药物治疗研究关键词：

BRAFV600E,联合治疗,类器官,乳头状甲状腺癌,治疗预测。

肿瘤治疗检测基因临床应用结果

靶向药物研究立项的依据：甲状腺乳头状癌 (PTC) 通常由 BRAF 基因的获得性体细胞突变驱动，是贼常见的甲状腺癌病理类型。 PTC经手术切除、甲状腺激素治疗和放射性碘辅助治疗等常规治疗后预后良好。不幸的是，大约 20% 的患者会出现局部反复或远处转移，这使得靶向治疗成为重要的治疗选择。目前的体外 PTC 模型在表现亲本肿瘤的细胞和突变特征方面受到限制。迫切需要一种预测个体治疗效果的临床相关工具。佳学基因解码的途径：将手术切除的 PTC 组织样本分离，接种到 Matrigel 中，并培养以产生类器官。随后分别对 PTC 类器官进行组织学分析、DNA 测序和药物敏感性测定。靶向药物研究的客观数据：我们建立了 9 个源自患者的 PTC 类器官模型，其中 5 个模型具有 BRAFV600E 突变。这些类器官已稳定培养超过 3 个月，并密切概括了各自原发性肿瘤的组织学结构和突变景观。 PTC 类器官培养物的药物敏感性测定证明了患者内和患者间的特异性药物反应。 BRAFV600E 抑制剂、vemurafenib 和 dabrafenib 单一疗法对治疗 BRAFV600E 突变型 PTC 类器官有一定疗效。尽管如此，与单独使用 BRAF 抑制剂相比，BRAF 抑制剂与 MEK 抑制剂、RTK 抑制剂或化学治疗剂的组合显示出更高的疗效。药物指导及病因判断的依据：这些数据表明，患者来源的 PTC 类器官可能是研究肿瘤生物学和药物反应性的有力研究工具，因此可用于验证或发现靶向药物组合。关键词：BRAFV600E；联合治疗；类器官；乳头状甲状腺癌；治疗预测。

肿瘤发生与革命国际数据库描述：

Backgrounds: Papillary thyroid cancer (PTC), which is often driven by acquired somatic mutations in BRAF genes, is the most common pathologic type of thyroid cancer. PTC has an excellent prognosis after treatment with conventional therapies such as surgical resection, thyroid hormone therapy and adjuvant radioactive iodine therapy. Unfortunately, about 20% of patients develop regional recurrence or distant metastasis, making targeted therapeutics an important treatment option. Current in vitro PTC models are limited in representing the cellular and mutational characteristics of parental tumors. A clinically relevant tool that predicts the efficacy of therapy for individuals is urgently needed.Methods: Surgically removed PTC tissue samples were dissociated, plated into Matrigel, and cultured to generate organoids. PTC organoids were subsequently subjected to histological analysis, DNA sequencing, and drug sensitivity assays, respectively.Results: We established 9 patient-derived PTC organoid models, 5 of which harbor BRAFV600E mutation. These organoids have been cultured stably for more than 3 months and closely recapitulated the histological architectures as well as mutational landscapes of the respective primary tumors. Drug sensitivity assays of PTC organoid cultures demonstrated the intra- and inter-patient specific drug responses. BRAFV600E inhibitors, vemurafenib and dabrafenib monotherapy was mildly effective in treating BRAFV600E-mutant PTC organoids. Nevertheless, BRAF inhibitors in combination with MEK inhibitors, RTK inhibitors, or chemotherapeutic agents demonstrated improved efficacy compared to BRAF inhibition alone.Conclusions: These data indicate that patient-derived PTC organoids may be a powerful research tool to investigate tumor biology and drug responsiveness, thus being useful to validate or discover targeted drug combinations.Keywords: BRAFV600E; Combination therapy; Organoid; Papillary thyroid cancer; Treatment prediction.