PARP Inhibitors: An Interesting Pathway also for Non-Small Cell Lung Cancer?

Author(s): Matteo Giaj Levra, Ken Andre Olaussen, Silvia Novello, Jean-Charles Soria.

Journal Name: Current Pharmaceutical Design

Volume 20 , Issue 24 , 2014

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Abstract:

Treatment of lung cancer is improving, also based on the identification of molecular characteristics of the tumor, of which some already constitute promising targets. One of the molecular characteristics thought to play an important role in lung cancer is DNA repair dysfunctionality. Deregulated expression of DNA repair proteins, such as PARP, has been studied in lung cancer as a possible biomarker and clinically useful target, but the literature remains relatively poor. Pharmacological inactivation of PARP has allowed the identification of a synthetic lethality with a second DNA repair protein such as BRCA1, but has also shown the potential to sensitize tumors to commonly used cytotoxic agents. The current manuscript reviews data regarding PARP in the context of DNA repair and its different pathways, as well as the clinical data generated until now with PARP inhibitors. A deeper understanding of the DNA damage response in lung malignancies, and particularly a clarification of the crosstalk between DNA repair functionality and genetic stability, is the key to optimize the development of PARP inhibitors in the setting of NSCLC.

Keywords: PARP1, lung cancer, synthetic lethality.

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Article Details

VOLUME: 20
ISSUE: 24
Year: 2014
Page: [3875 - 3882]
Pages: 8
DOI: 10.2174/13816128113196660765
Price: $58

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