Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation
// Francesco Paolo Fiorentino 1 , Elvan Tokgün 1 , Sònia Solé-Sánchez 1 , Sabrina Giampaolo 1 , Onur Tokgün 1 , Toni Jauset 2 , Takashi Kohno 3 , Manuel Perucho 1, 4 , Laura Soucek 2, 4, 5 , Jun Yokota 1, 3 1 Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Campus Can Ruti, Barcelona, Spain 2 Vall d’Hebron Institute of Oncology (VHIO) Hospital Vall d’Hebron, Barcelona, Spain 3 Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan 4 Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain 5 Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain Correspondence to: Jun Yokota, e-mail: jyokota@imppc.org Keywords: small cell lung cancer, MYC, CDKN1A, MYCL, SCLC Received: February 18, 2016     Accepted: March 31, 2016     Published: April 18, 2016 ABSTRACT 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.