1. New therapeutic perspectives in CCDC6 deficient lung cancer cells
- Author
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Morra, F, Luise, C, Visconti, R, Staibano, S, Merolla, Francesco, 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, Mt, Celetti, A., Morra, F, Luise, C, Visconti, R, Staibano, Stefania, Merolla, F, Ilardi, Gennaro, Guggino, G, Paladino, Simona, Sarnataro, Daniela, Franco, R, Monaco, R, Zitomarino, F, Pacelli, Roberto, Monaco, G, Rocco, G, Cerrato, A, Linardopoulos, S, Muller, Mt, and Celetti, A.
- Subjects
Male ,Resistance to platinum salts and PARP-1 inhibitor sensitivity ,DNA Repair ,POLY(ADP-RIBOSE) POLYMERASE ,NSCLC ,Disease-Free Survival ,Candidate biomarker ,Antineoplastic Agent ,Author Keywords:NSCLC ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Cytoskeletal Protein ,resistance to platinum salts and PARP-1 inhibitor sensitivity KeyWords Plus:HOMOLOGY-DIRECTED REPAIR ,CCDC6 ,DNA damage and homologous-directed repair ,candidate biomarker ,BRCA MUTATION CARRIERS ,DNA-REPAIR ,SENSITIVITY ,RET ,ADENOCARCINOMA ,CHEMOTHERAPY ,RESISTANCE ,INHIBITORS ,Piperazine ,Aged ,Phthalazine ,Aged, 80 and over ,Apoptosi ,Lymphatic Metastasi ,Middle Aged ,Lung Neoplasm ,Female ,Rad51 Recombinase ,Cisplatin ,DNA damage and homologousdirected repair ,DNA Damage ,Human - 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-coil-domain 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
- Published
- 2014