New therapeutic perspectives in CCDC6 deficient lung cancer cells

Francesco Morra, Chiara Luise, Roberta Visconti, Stefania Staibano, Francesco Merolla, Gennaro Ilardi, Gianluca Guggino, Simona Paladino, Daniela Sarnataro, Renato Franco, Roberto Monaco, Federica Zitomarino, Roberto Pacelli, Guglielmo Monaco, Gaetano Rocco, Aniello Cerrato, Spiros Linardopoulos, Mark T. Muller, Angela Celetti

Research output: Contribution to journalArticle

Abstract

Non-small cell lung cancer (NSCLC) is the main cause of cancer-related death worldwide and new therapeutic strategies are urgently needed. In this study, we have characterized a panel of NSC lung cancer cell lines for the expression of coiled-coildomain containing 6 (CCDC6), a tumor suppressor gene involved in apoptosis and DNA damage response. We show that low CCDC6 protein levels are associated with a weak response to DNA damage and a low number of Rad51 positive foci. Moreover, CCDC6 deficient lung cancer cells show defects in DNA repair via homologous recombination. In accordance with its role in the DNA damage response, CCDC6 attenuation confers resistance to cisplatinum, the current treatment of choice for NSCLC, but sensitizes the cells to olaparib, a small molecule inhibitor of the repair enzymes PARP1/2. Remarkably, the combination of the two drugs is more effective than each agent individually, as demonstrated by a combination index

Original languageEnglish
Pages (from-to)2146-2157
Number of pages12
JournalInternational Journal of Cancer
Volume136
Issue number9
DOIs
Publication statusPublished - May 1 2015

Keywords

  • Candidate biomarker
  • CCDC6
  • DNA damage and homologousdirected repair
  • NSCLC
  • Resistance to platinum salts and PARP-1 inhibitor sensitivity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Morra, F., Luise, C., Visconti, R., Staibano, S., Merolla, F., Ilardi, G., Guggino, G., Paladino, S., Sarnataro, D., Franco, R., Monaco, R., Zitomarino, F., Pacelli, R., Monaco, G., Rocco, G., Cerrato, A., Linardopoulos, S., Muller, M. T., & Celetti, A. (2015). New therapeutic perspectives in CCDC6 deficient lung cancer cells. International Journal of Cancer, 136(9), 2146-2157. https://doi.org/10.1002/ijc.29263