誠信認證:
工商注冊信息已核實!領域: | 分子生物學,蛋白/抗體/蛋白質組,多組學/蛋白質組/代謝組/脂質組 | ||
樣品: | 臨床肺腺癌樣本 | 項目: | KRAS陽性,KRAS陰性 |
參考: | PNAS,2017,vol. 114,no. 17。 |
方案文件名 | 下載 |
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PNAS報道 KRAS相關ERK活性圖譜與肺腺癌精準治療 |
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肺腺癌( lung adenocarcinoma )是肺癌的一種,屬于非小細胞癌。雖然已經有多種免疫療法已經EGFR靶向治療藥物在臨床上使用,但是療效欠佳。
已知KRAS基因突變是引起肺腺癌重要因素。而KRAS-ERK-脂肪合成信號通路激活與肺腺癌惡性程度密切相關,因而圍繞KARS活化及脂肪合成代謝研究,以發現新的診斷和治療策略獲得了眾多基礎和臨床科學家的關注。
最近著名雜志PNAS發表了美國斯坦福大學醫學院腫瘤學系及德克薩斯大學生化系合作工作:Oncogene KRAS activates fatty acid synthase, resulting inspecific ERK and lipid signatures associated with lung adenocarcinoma. 4300–4305,PNAS,2017,vol. 114,no. 17。
文章最主要工作之一,作者使用ProteinSimple Nanopro1000納米級免疫檢測(nanoimmunoassay (NIA)),系統,建立KARS相關ERK(extracellular regulated protein kinases)活化圖譜。作者發現,KARS陽性腫瘤特異性出現ERK2磷酸化圖譜增強,KRAS陰性腫瘤則特異性出現ERK1磷酸化圖譜增強。
NIA ERK protein signatures: (A) normal vs. humanKRAS-associated lung cancer tissue (n = 6), (B) normal vs. human non-KRAS lung cancer tissue (n = 6), and percentages oftotal ERK in (C) KRAS tumors and (D) non-KRAS tumors.*Statistical significance by t test for P value <0.05. **Statistical significance by t test for P value <0.01.
作者特別強調了使用Nanopro1000納米級免疫分析系統在癌癥精準診斷治療中的意義:
極高靈敏度,可以在微量臨床樣本中檢測蛋白磷酸化圖譜變化
獨特的蛋白質磷酸化圖譜檢測,有助于基于此開發相關藥物及選擇臨床治療方案
We identified unique proteomic and lipid signatures of KRAS lung adenocarcinoma.By NIA, ERK1 vs. ERK2 protein activation allowed us to distinguish betweenKRAS-positive and -negative tumors in clinical specimens. NIA is a highly sensitive nanofluidic approach that is highly tractable for the examination ofeven picograms of protein derived from as few as 20 cells to measure proteins andtheir phosphorylation state (40, 41). Thus, NIA measurement of ERK may beuseful in the diagnosis of lung adenocarcinoma.
作者接下來的工作將是在臨床研究中,選擇靶向KRAS-ERK-脂肪合成途徑的藥物,治療對于免疫治療及EGFR靶向治療不敏感的病人。
Ourresults suggest that KRAS-induced lung adenocarcinoma may be particularlysusceptible to the targeted therapeutic inhibition of FASN (acid synthase(FASN).) . More clinical workis needed to verify this hypothesis.
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