Journal
CANCER RESEARCH
Volume 73, Issue 7, Pages 2271-2280Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-12-3000
Keywords
-
Categories
Funding
- European Commission (ArtForce)
- Agence National de la Recherche (ANR)
- Ligue contre le Cancer (Equipe labellisee)
- Fondation pour la Recherche Medicale (FRM)
- Institut National du Cancer (INCa)
- LabEx Immuno-Oncologie
- Fondation de France
- Fondation Bettencourt-Schueller
- AXA Chair for Longevity Research
- Canceropole Ile-de-France and Paris Alliance of Cancer Research Institutes (PACRI)
- French Ministry of Science
- FRM
- Groupe Pasteur Mutualite
- Action Lions Vaincre le Cancer (Luxembourg)
- Ligue Nationale contre le Cancer
- Fondation ARC pour la Recherche sur le Cancer
Ask authors/readers for more resources
Non-small cell lung carcinoma patients are frequently treated with cisplatin (CDDP), most often yielding temporary clinical responses. Here, we show that PARP1 is highly expressed and constitutively hyperactivated in a majority of human CDDP-resistant cancer cells of distinct histologic origin. Cells manifesting elevated intracellular levels of poly(ADP-ribosyl)ated proteins (PAR(high)) responded to pharmacologic PARP inhibitors as well as to PARP1-targeting siRNAs by initiating a DNA damage response that translated into cell death following the activation of the intrinsic pathway of apoptosis. Moreover, PARP1-overexpressing tumor cells and xenografts displayed elevated levels of PAR, which predicted the response to PARP inhibitors in vitro and in vivo more accurately than PARP1 expression itself. Thus, a majority of CDDP-resistant cancer cells appear to develop a dependency to PARP1, becoming susceptible to PARP inhibitor-induced apoptosis. Cancer Res; 73(7); 2271-80. (C)2013 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available