New therapeutic perspectives in CCDC6 deficient lung cancer cells

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...

Full description

Saved in:
Bibliographic Details
Published in:International journal of cancer 2015-05, Vol.136 (9), p.2146-2157
Main Authors: Morra, Francesco, Luise, Chiara, Visconti, Roberta, Staibano, Stefania, Merolla, Francesco, Ilardi, Gennaro, Guggino, Gianluca, Paladino, Simona, Sarnataro, Daniela, Franco, Renato, Monaco, Roberto, Zitomarino, Federica, Pacelli, Roberto, Monaco, Guglielmo, Rocco, Gaetano, Cerrato, Aniello, Linardopoulos, Spiros, Muller, Mark T., Celetti, Angela
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Apoptosis - genetics
Cancer
Cancer therapies
candidate biomarker
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - genetics
CCDC6
Cell Line, Tumor
Cisplatin - pharmacology
Cytoskeletal Proteins - deficiency
Cytoskeletal Proteins - genetics
Deoxyribonucleic acid
Disease-Free Survival
DNA
DNA damage
DNA Damage - drug effects
DNA Damage - genetics
DNA damage and homologous‐directed repair
DNA repair
DNA Repair - drug effects
DNA Repair - genetics
Female
Humans
Lung cancer
Lung Neoplasms - drug therapy
Lung Neoplasms - genetics
Lymphatic Metastasis - genetics
Male
Medical research
Middle Aged
NSCLC
Phthalazines
Piperazines
Rad51 Recombinase - genetics
resistance to platinum salts and PARP‐1 inhibitor sensitivity
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.29263