Molecular biology of lung cancer: clinical implications.
Molecular biology of lung cancer: clinical implications.
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DOI：
10.1016/j.ccm.2011.08.003
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发表时间：
2011-12
影响因子：
5.7
通讯作者：
Minna JD
中科院分区：
文献类型：
--
作者：
Larsen JE;Minna JD
肺癌是美国男性和女性癌症相关死亡的主要原因，占2010年癌症死亡总数的约28%，尽管仅占新发癌症病例的约15%1。几十年的研究帮助我们理解了肺癌是一个涉及遗传和表观遗传学改变的多步骤过程，由此导致的DNA损伤将正常肺上皮细胞转化为肺CAncer2，3。目前尚不清楚是所有肺上皮细胞还是只有这些细胞的一部分(如肺上皮干细胞或其直系祖细胞)容易完全恶性转化。此外，虽然肿瘤起始细胞可能只有几个突变，但随着肿瘤的扩大，细胞可能会获得更多的突变。吸烟损害整个呼吸道上皮，因此在组织学上正常的肺上皮以及各种组织学癌前/癌前病变中观察到“野癌变”或“野缺陷”(分子变化)，这些病变也具有与邻近肿瘤相同的分子异常5。这些变化的结果导致肺癌表现出所有的癌症特征(包括生长信号的自给自足、对生长抑制(抗生长)信号的不敏感、逃避细胞程序性死亡(细胞凋亡)、无限复制潜力、持续的血管生成以及组织侵袭和转移)6、7.肺癌是一种临床、生物学、组织学和分子方面的异质性疾病。了解这种异质性的分子原因是当前研究的重点，这些原因可能反映了不同类别的上皮细胞发生的变化，或者反映了同一靶肺上皮细胞发生的不同分子变化。识别涉及的基因和途径，确定它们与肺癌生物学行为的关系，以及它们作为诊断和治疗靶点的有效性，是重要的基础和翻译研究问题。因此，关于肺癌发病机制中的关键分子步骤及其在癌前病变、原发癌和转移性疾病中的时机及其临床意义的最新信息是本综述的主题。
Lung cancer is the leading cause of cancer-related death in men and women in the United States accounting for approximately 28% of total cancer deaths in 2010 despite comprising only~ 15% of new cancer cases1. Decades of research have contributed to our understanding that lung cancer is a multi-step process involving genetic and epigenetic alterations where resulting DNA damage transforms normal lung epithelial cells into lung cancer2, 3. It is not known whether all lung epithelial cells or only a subset of these cells (such as pulmonary epithelial stem cells or their immediate progenitors) are susceptible to full malignant transformation. Additionally, while the tumor initiating cell may have only a handful of mutations, as the tumor expands cells may acquire additional mutations4. Smoking damages the entire respiratory epithelium and thus “field cancerization” or “field defects”(molecular changes) are observed in histologically normal lung epithelium, as well as a variety of histologic preneoplastic/premalignant lesions, which also harbor molecular abnormalities common to the adjacent tumor5. The culmination of these changes leads to lung cancers exhibiting all the “hallmarks of cancer”(including self-sufficiency of growth signals, insensitivity to growth-inhibitory (anti-growth) signals, evasion of programmed cell death (apoptosis), limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis) 6, 7. Lung cancer is a heterogeneous disease clinically, biologically, histologically and molecularly. Understanding the molecular causes of this heterogeneity is the focus of current research and these could reflect changes occurring in different classes of epithelial cells or different molecular changes occurring in the same target lung epithelial cells. Identifying the genes and pathways involved, determining how they relate to the biologic behavior of lung cancer and their utility as diagnostic and therapeutic targets are important basic and translational research issues. Thus, current information on the key molecular steps in lung cancer pathogenesis and their timing in preneoplasia, primary cancer, and metastatic disease and the clinical implications is the subject of this review.
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影响因子：
3.5
作者：
Baylin, SB;Esteller, M;Herman, JG
通讯作者：
Herman, JG
影响因子：
30.8
作者：
Bass, Adam J.;Watanabe, Hideo;Mermel, Craig H.;Yu, Soyoung;Perner, Sven;Verhaak, Roel G.;Kim, So Young;Wardwell, Leslie;Tamayo, Pablo;Gat-Viks, Irit;Ramos, Alex H.;Woo, Michele S.;Weir, Barbara A.;Getz, Gad;Beroukhim, Rameen;O'Kelly, Michael;Dutt, Amit;Rozenblatt-Rosen, Orit;Dziunycz, Piotr;Komisarof, Justin;Chirieac, Lucian R.;LaFargue, Christopher J.;Scheble, Veit;Wilbertz, Theresia;Ma, Changqing;Rao, Shilpa;Nakagawa, Hiroshi;Stairs, Douglas B.;Lin, Lin;Giordano, Thomas J.;Wagner, Patrick;Minna, John D.;Gazdar, Adi F.;Zhu, Chang Qi;Brose, Marcia S.;Cecconello, Ivan;Ribeiro, Ulysses, Jr.;Marie, Suely K.;Dahl, Olav;Shivdasani, Ramesh A.;Tsao, Ming-Sound;Rubin, Mark A.;Wong, Kwok K.;Regev, Aviv;Hahn, William C.;Beer, David G.;Rustgi, Anil K.;Meyerson, Matthew
通讯作者：
Meyerson, Matthew
DOI：
10.1016/s1357-2725(97)00007-1
发表时间：
1997-12-01
影响因子：
4
作者：
Bingle, CD
通讯作者：
Bingle, CD
影响因子：
11.2
作者：
Broderick P;Wang Y;Vijayakrishnan J;Matakidou A;Spitz MR;Eisen T;Amos CI;Houlston RS
通讯作者：
Houlston RS
DOI：
10.1073/pnas.0710370104
发表时间：
2007-12-26
影响因子：
11.1
作者：
Bean, James;Brennan, Cameron;Pao, William
通讯作者：
Pao, William