加州大学洛杉矶分校Thomas G. Graeber研究团队取得进展。他们提出了泛癌会聚为小细胞神经内分泌表型，与血液学恶性肿瘤具有相同的敏感性。 该研究于2019年7月8日发表于国际一流学术期刊《癌细胞》上。

小组确定了一种SCN会聚状态，这种状态在上皮癌中广泛存在，并且与预后不良有关。从更广泛的意义上讲，非SCN转移瘤比非SCN原发肿瘤具有更高的SCN相关转录因子表达水平。药物敏感性和基因依赖性筛选表明这些会聚的SCNCs具有共同的弱点。在没有注释的SCN类似上皮病例，小圆蓝细胞肿瘤，和出乎意料的血液学恶性肿瘤都发现了这些共同的弱点。SCN会聚表型和与血液学肿瘤相同的敏感特征可以成为组织特异性靶向治疗之外的治疗指导方案。

据介绍，小细胞神经内分泌癌(SCNCs)是一种侵袭性肿瘤亚型。向SCN表型的转分化已被报道为一种针对靶向治疗的耐药途径。

附：英文原文

Title: Pan-cancer Convergence to a Small-Cell Neuroendocrine Phenotype that Shares Susceptibilities with Hematological Malignancies

Author: Nikolas G. Balanis, Katherine M. Sheu, Favour N. Esedebe, Saahil J. Patel, Bryan A. Smith, Jung Wook Park, Salwan Alhani, Brigitte N. Gomperts, Jiaoti Huang, Owen N. Witte, Thomas G. Graeber

Issue&Volume: Jul 08, 2019 Volume 36Issue 1

Abstract: Small-cell neuroendocrine cancers (SCNCs) are an aggressive cancer subtype. Transdifferentiation toward an SCN phenotype has been reported as a resistance route in response to targeted therapies. Here, we identified a convergence to an SCN state that is widespread across epithelial cancers and is associated with poor prognosis. More broadly, non-SCN metastases have higher expression of SCN-associated transcription factors than non-SCN primary tumors. Drug sensitivity and gene dependency screens demonstrate that these convergent SCNCs have shared vulnerabilities. These common vulnerabilities are found across unannotated SCN-like epithelial cases, small-round-blue cell tumors, and unexpectedly in hematological malignancies. The SCN convergent phenotype and common sensitivity profiles with hematological cancers can guide treatment options beyond tissue-specific targeted therapies.

DOI: https://doi.org/10.1016/j.ccell.2019.06.005

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30296-X