Data from Cisplatin Resistance Associated with PARP Hyperactivation
Year: 2023
Type: other
Abstract: 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 (PARhigh) 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. ©2013 AACR.
Authors: Judith Michels, Ilio Vitale, Lorenzo Galluzzi, Julien Adam, Ken André Olaussen, Oliver Kepp, Laura Senovilla, Ibtissam Talhaoui, Justine Guegan, David Pierre Enot, Monique Talbot, Angélique Robin, Philippe Girard, Cédric Oréar, Delphine Lissa, Abdul Qader Sukkurwala, Pauline Garcia, Parviz Behnam-Motlagh, Kimitoshi Kohno, Gen Sheng Wu, Catherine Brenner, Philippe Dessen, Murat Saparbaev, Jean-Charles Soria, Maria Castedo, Guido Kroemer
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4392687477