Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA 90095, USA.
Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA 90095, USA.
Cancer Cell. 2019 Jul 8;36(1):17-34.e7. doi: 10.1016/j.ccell.2019.06.005.
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.
小细胞神经内分泌癌（SCNC）是一种侵袭性癌症亚型。已有报道称，向 SCN 表型的转化是对靶向治疗产生耐药性的途径之一。在这里，我们发现一种广泛存在于上皮癌中的向 SCN 状态的趋同现象，并且与预后不良相关。更广泛地说，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。药物敏感性和基因依赖性筛选表明，这些趋同的 SCNC 具有共同的弱点。这些共同的弱点在未注释的 SCN 样上皮病例、小圆细胞蓝色肿瘤中均有发现，出乎意料的是在血液恶性肿瘤中也有发现。SCN 趋同表型和与血液癌症的共同敏感性特征可以指导超出组织特异性靶向治疗的治疗选择。
