基因组和基因表达研究有助于确定小细胞肺癌癌症和其他肺部神经内分泌肿瘤的异质性,并确定新的治疗靶点

Onco Pub Date : 2022-08-15 DOI:10.3390/onco2030013
U. Testa, E. Pelosi, G. Castelli
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引用次数: 0

摘要

癌症小细胞肺癌(SCLC)是一种高度神经内分泌癌,约占肺癌的15%,主要发生在吸烟者中,预后极差。在SCLC中经常观察到的关键基因改变表现为由于突变事件或缺失导致的TP53和RB1的缺失;MYC家族基因(MYC、MYCL和MYCN)的频繁扩增或过表达;KMT2D、RB家族成员p107(RBL1)和p130(RBL2)、PTEN、NOTCH受体和CREBBP的突变/缺失引起的频繁遗传改变。特异性转录因子的表达谱允许区分根据ASCL1(SCLC-A)、NEUROD1(SCLC-N)、POUF23(SCLC-P)或YAP1(SCLC-Y)水平定义的四种SCLC亚型。最近的一项研究确定了SCLC-I亚组,其特征是炎症/免疫相关基因的表达。最近的研究在分子水平上表征了其他肺神经内分泌肿瘤,包括大细胞神经内分泌癌(LCNECs)和类肺癌。这些分子研究已经确定了一些治疗漏洞,可以使用特定的药物和一些有前景的生物标志物来预测对这种治疗的反应。此外,将免疫疗法(免疫检查点阻断)引入标准一线治疗,在有限的患者中带来了显著的临床益处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genomic and Gene Expression Studies Helped to Define the Heterogeneity of Small-Cell Lung Cancer and Other Lung Neuroendocrine Tumors and to Identify New Therapeutic Targets
Small-cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma, corresponding to about 15% of lung cancers, occurring predominantly in smokers and associated with a very poor prognosis. Key genetic alterations very frequently observed in SCLC are represented by the loss of TP53 and RB1, due to mutational events or deletions; frequent amplification or overexpression of MYC family genes (MYC, MYCL and MYCN); frequent genetic alterations by mutation/deletion of KMT2D, RB family members p107 (RBL1) and p130 (RBL2), PTEN, NOTCH receptors and CREBBP. The profile of expression of specific transcription factors allowed to differentiate four subtypes of SCLC defined according to levels of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POUF23 (SCLC-P) or YAP1 (SCLC-Y). A recent study identified the subgroup SCLC-I, characterized by the expression of inflammatory/immune-related genes. Recent studies have characterized at molecular level other lung neuroendocrine tumors, including large cell neuroendocrine cancers (LCNECs) and lung carcinoids. These molecular studies have identified some therapeutic vulnerabilities that can be targeted using specific drugs and some promising biomarkers that can predict the response to this treatment. Furthermore, the introduction of immunotherapy (immune checkpoint blockade) into standard first-line treatment has led to a significant clinical benefit in a limited subset of patients.
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