Research Papers:

Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation

Francesco Paolo Fiorentino, Elvan Tokgün, Sònia Solé-Sánchez, Sabrina Giampaolo, Onur Tokgün, Toni Jauset, Takashi Kohno, Manuel Perucho, Laura Soucek and Jun Yokota _

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Oncotarget. 2016; 7:31014-31028. https://doi.org/10.18632/oncotarget.8826

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Francesco Paolo Fiorentino1, Elvan Tokgün1, Sònia Solé-Sánchez1, Sabrina Giampaolo1, Onur Tokgün1, Toni Jauset2, Takashi Kohno3, Manuel Perucho1,4, Laura Soucek2,4,5, Jun Yokota1,3

1Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Campus Can Ruti, Barcelona, Spain

2Vall d’Hebron Institute of Oncology (VHIO) Hospital Vall d’Hebron, Barcelona, Spain

3Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan

4Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain

5Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain

Correspondence to:

Jun Yokota, e-mail: [email protected]

Keywords: small cell lung cancer, MYC, CDKN1A, MYCL, SCLC

Received: February 18, 2016    Accepted: March 31, 2016    Published: April 18, 2016


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.

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