Fiorentino Francesco Paolo, Tokgün Elvan, Solé-Sánchez Sònia, Giampaolo Sabrina, Tokgün Onur, Jauset Toni, Kohno Takashi, Perucho Manuel, Soucek Laura, Yokota Jun
Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Campus Can Ruti, Barcelona, Spain.
Vall d'Hebron Institute of Oncology (VHIO) Hospital Vall d'Hebron, Barcelona, Spain.
Oncotarget. 2016 May 24;7(21):31014-28. doi: 10.18632/oncotarget.8826.
Small cell lung cancer (SCLC) is the most aggressive type of lung cancer with high mortality. One of the MYC family genes, MYC, MYCL or MYCN, is amplified in ~20% of the SCLCs; therefore, MYC proteins are potential therapeutic targets in SCLC patients. We investigated the therapeutic impact of Omomyc, a MYC dominant negative, in a panel of SCLC cell lines. Strikingly, Omomyc suppressed the growth of all tested cell lines by inducing cell cycle arrest and/or apoptosis. Induction of G1 arrest by Omomyc was found to be dependent on the activation of CDKN1A, in part, through the TP73 pathway. Our results strongly indicate that SCLC cells carrying amplification of MYC, MYCL or MYCN are addicted to MYC function, suggesting that MYC targeting would be an efficient therapeutic option for SCLC patients.
小细胞肺癌（SCLC）是最具侵袭性的肺癌类型，死亡率很高。在约20%的小细胞肺癌中，MYC家族基因之一，即MYC、MYCL或MYCN会发生扩增；因此，MYC蛋白是小细胞肺癌患者潜在的治疗靶点。我们研究了MYC显性负性蛋白Omomyc对一组小细胞肺癌细胞系的治疗作用。令人惊讶的是，Omomyc通过诱导细胞周期停滞和/或凋亡抑制了所有测试细胞系的生长。发现Omomyc诱导G1期停滞部分依赖于CDKN1A的激活，通过TP73途径实现。我们的结果有力地表明，携带MYC、MYCL或MYCN扩增的小细胞肺癌细胞对MYC功能有依赖性，这表明靶向MYC将是小细胞肺癌患者一种有效的治疗选择。
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