【佳學(xué)基因靶向藥物基因檢測(cè)】攜帶 BRAFV600E 突變的甲狀腺乳頭狀癌類器官揭示了基于 BRAF 抑制劑的聯(lián)合療法的潛在有益作用

基因治療腫瘤方法賊新簡(jiǎn)介

研討三甲醫(yī)師職稱提升腫瘤學(xué)在《腫瘤診斷基因與轉(zhuǎn)移分析》收錄《J Transl Med》在?2023 Jan 9;21(1):9.發(fā)表了一篇題目為《》腫瘤靶向藥物治療基因檢測(cè)臨床研究文章。該研究由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。促進(jìn)了腫瘤的正確治療與個(gè)性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測(cè)與分析的重要性。

腫瘤基因檢測(cè)及靶向藥物治療研究關(guān)鍵詞：

BRAFV600E,聯(lián)合治療,類器官,乳頭狀甲狀腺癌,治療預(yù)測(cè)。

腫瘤治療檢測(cè)基因臨床應(yīng)用結(jié)果

靶向藥物研究立項(xiàng)的依據(jù)：甲狀腺乳頭狀癌 (PTC) 通常由 BRAF 基因的獲得性體細(xì)胞突變驅(qū)動(dòng)，是賊常見(jiàn)的甲狀腺癌病理類型。 PTC經(jīng)手術(shù)切除、甲狀腺激素治療和放射性碘輔助治療等常規(guī)治療后預(yù)后良好。不幸的是，大約 20% 的患者會(huì)出現(xiàn)局部反復(fù)或遠(yuǎn)處轉(zhuǎn)移，這使得靶向治療成為重要的治療選擇。目前的體外 PTC 模型在表現(xiàn)親本腫瘤的細(xì)胞和突變特征方面受到限制。迫切需要一種預(yù)測(cè)個(gè)體治療效果的臨床相關(guān)工具。佳學(xué)基因解碼的途徑：將手術(shù)切除的 PTC 組織樣本分離，接種到 Matrigel 中，并培養(yǎng)以產(chǎn)生類器官。隨后分別對(duì) PTC 類器官進(jìn)行組織學(xué)分析、DNA 測(cè)序和藥物敏感性測(cè)定。靶向藥物研究的客觀數(shù)據(jù)：我們建立了 9 個(gè)源自患者的 PTC 類器官模型，其中 5 個(gè)模型具有 BRAFV600E 突變。這些類器官已穩(wěn)定培養(yǎng)超過(guò) 3 個(gè)月，并密切概括了各自原發(fā)性腫瘤的組織學(xué)結(jié)構(gòu)和突變景觀。 PTC 類器官培養(yǎng)物的藥物敏感性測(cè)定證明了患者內(nèi)和患者間的特異性藥物反應(yīng)。 BRAFV600E 抑制劑、vemurafenib 和 dabrafenib 單一療法對(duì)治療 BRAFV600E 突變型 PTC 類器官有一定療效。盡管如此，與單獨(dú)使用 BRAF 抑制劑相比，BRAF 抑制劑與 MEK 抑制劑、RTK 抑制劑或化學(xué)治療劑的組合顯示出更高的療效。藥物指導(dǎo)及病因判斷的依據(jù)：這些數(shù)據(jù)表明，患者來(lái)源的 PTC 類器官可能是研究腫瘤生物學(xué)和藥物反應(yīng)性的有力研究工具，因此可用于驗(yàn)證或發(fā)現(xiàn)靶向藥物組合。關(guān)鍵詞：BRAFV600E；聯(lián)合治療；類器官；乳頭狀甲狀腺癌；治療預(yù)測(cè)。

腫瘤發(fā)生與革命國(guó)際數(shù)據(jù)庫(kù)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.