Deeper understanding of the pathobiology of non-small

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Deeper understanding of the pathobiology of non-small

cell lung cancer(NSCLC) has led to the development of small molecules that target genetic mutations known to play critical roles in progression to metastatic disease and to influence response to targeted therapies. The principle goal of precision medicine is to define those patient populations most likely to respond to targeted therapies. However, the cancer genome microtubule phosphorylation landscape is composed of relatively few “mountains” [representing the most commonly mutated genes like KRAS, epidermal growth factor(EGFR), and anaplastic lymphoma 寻找更多 kinase(ALK)] and a vast number of “hills”(representing low frequency but potentially actionable mutations). Low-frequency lesions that affect a druggable gene product allow a relatively small population of cancer patients for targeted therapy to be selected.
2009年美国临床肿瘤学会(American

Society of Clinical Oncology,ASCO)报道一种全新的分子靶向药物可选择性抑制DNA修复相关的关键酶——聚腺苷二磷酸核糖聚合酶-1[poly(ADP-ribose)polymerase-1,PARP-1],对三阴乳腺癌患者有效。这一突破性成果强烈预示以DNA损伤修复通路为靶标的分子治疗可能成为肿瘤治疗的新策略。DNA损伤修复是细胞
目的:研究非小细胞肺癌患者的间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)融合基因的表达情况和临床病理特点。方法:从北京大学第三医院随机选择了有随访资料的95例非小细胞肺癌患者,采用ALK+插入式抗体强化免疫组织化学法(intercalated

antibody-enhanced selleck产品 polymer,iAEP)和荧光原位杂交技术(fluorescence in situ hybridization,FISH)检测患者ALK融合基因的表达情况,并分析ALK融合基因阳性患者的临床病理特点、生存期和EGFR/KRAS基因突变情况。结果:采用ALK+iAEP法共筛选出8例ALK阳性病例,其中4例经FISH法证实存在ALK融合基因,检出率为4.2%(4/95),其中2例女性肺癌患者的组织学类型是实体性肺腺癌伴印戒细胞形态,另2例男性肺癌患者是腺鳞癌。4例肺癌患者中3例为非吸烟者,均无EGFR/KRAS基因突变,且均存活,其中有2例患者已存活超过5年。结论:ALK+iAEP法较常规ALK免疫组织化学法能明显提高肺癌患者ALK的检出率,可以作为初筛ALK阳性病例的方法,且阳性细胞的比例较阳性强度更重要。ALK融合基因在非小细胞肺癌患者中的检出率较低(<5%),同时可能提示预后较好。
棘皮动物微管结合蛋白4(echinoderm microtubule associated protein-like 4,EML4)与间变淋巴瘤激酶(anaplastic lymphoma kinase,ALK)形成的融合基因,被认为是非小细胞肺癌(NSCLC)新的分子靶点。EML4-ALK融合基因的发生率为3%~11%,该融合基因在年轻、腺癌、不吸烟或轻度吸烟的NSCLC患者中发生率较高,表达阳性者可以受益于ALK抑制剂(如克唑替尼)的治疗。本文重点阐述NSCLC中EML4-ALK融合基因的生物学特性、检测方法、临床特征和治疗方式。
目的研究克里唑替尼的合成工艺。方法以2,6-二氯-3-氟苯乙酮为起始原料,经还原、手性拆分、Mitsunobu反应、还原、溴代得中间体(R)-5-溴-3-(1-(2,6-二氯-3-氟苯基)乙氧基)-吡啶-2-胺,然后该中间体与1-(N-Boc-4-哌啶基)吡唑-4-硼酸频哪醇酯经Suzuki反应、脱除Boc保护基得到目标化合物克里唑替尼。结果与结论目标化合物的结构经1H-NMR、13C-NMR、MS及IR确证。总收率达14.

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