对表皮生长因子受体（EGFR）突变的耐药性肺腺癌转化为小细胞肺癌过程中的RB基因缺失。
RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer.
作者信息
Niederst Matthew J, Sequist Lecia V, Poirier John T, Mermel Craig H, Lockerman Elizabeth L, Garcia Angel R, Katayama Ryohei, Costa Carlotta, Ross Kenneth N, Moran Teresa, Howe Emily, Fulton Linnea E, Mulvey Hillary E, Bernardo Lindsay A, Mohamoud Farhiya, Miyoshi Norikatsu, VanderLaan Paul A, Costa Daniel B, Jänne Pasi A, Borger Darrell R, Ramaswamy Sridhar, Shioda Toshi, Iafrate Anthony J, Getz Gad, Rudin Charles M, Mino-Kenudson Mari, Engelman Jeffrey A
机构信息
1] Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA [2] Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA.
Memorial Sloan Kettering Cancer Center, Thoracic Oncology Service, 1275 York Avenue, New York, New York 10065, USA.
出版信息
Nat Commun. 2015 Mar 11;6:6377. doi: 10.1038/ncomms7377.
Tyrosine kinase inhibitors are effective treatments for non-small-cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) mutations. However, relapse typically occurs after an average of 1 year of continuous treatment. A fundamental histological transformation from NSCLC to small-cell lung cancer (SCLC) is observed in a subset of the resistant cancers, but the molecular changes associated with this transformation remain unknown. Analysis of tumour samples and cell lines derived from resistant EGFR mutant patients revealed that Retinoblastoma (RB) is lost in 100% of these SCLC transformed cases, but rarely in those that remain NSCLC. Further, increased neuroendocrine marker and decreased EGFR expression as well as greater sensitivity to BCL2 family inhibition are observed in resistant SCLC transformed cancers compared with resistant NSCLCs. Together, these findings suggest that this subset of resistant cancers ultimately adopt many of the molecular and phenotypic characteristics of classical SCLC.
酪氨酸激酶抑制剂是治疗具有表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）的有效方法。然而，通常在连续治疗平均1年后会出现复发。在一部分耐药癌症中观察到从NSCLC到小细胞肺癌（SCLC）的基本组织学转变，但与这种转变相关的分子变化仍然未知。对来自耐药EGFR突变患者的肿瘤样本和细胞系进行分析发现，在这些转化为SCLC的病例中，100%出现视网膜母细胞瘤（RB）缺失，而在那些仍为NSCLC的病例中则很少见。此外，与耐药NSCLC相比，在耐药的转化为SCLC的癌症中观察到神经内分泌标志物增加、EGFR表达降低以及对BCL2家族抑制的敏感性更高。这些发现共同表明，这部分耐药癌症最终呈现出许多经典SCLC的分子和表型特征。
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