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Lung cancer

Enhancer of zeste homolog 2 (EZH2); poly(ADP-ribose) polymerase-1 (PARP-1)

A study in cell culture and in patient tissue suggests inhibiting PARP-1 or EZH2 could help treat small cell lung cancer (SCLC). SCLC cell lines expressed higher protein levels of PARP-1 and EZH2 than non-small cell lung cancer (NSCLC) cell lines. Tumor tissue from patients with SCLC had higher levels of PARP-1 protein than tumor tissue from patients with NSCLC. In SCLC cell lines, a PARP-1 inhibitor or small hairpin RNA against PARP-1 or EZH2 decreased cell proliferation compared with no treatment or control shRNA. Next steps could include testing PARP-1 or EZH2 inhibitors in mouse models of SCLC.
At least 10 companies have preclinical or clinical programs targeting PARP-1 for cancer.
Epizyme Inc. and partner Eisai Co. Ltd. have a preclinical program targeting EZH2 in breast cancer and non-Hodgkin's lymphoma (NHL).
Constellation Pharmaceuticals Inc. has a discovery-stage program targeting EZH2 in cancer.

SciBX 5(39); doi:10.1038/scibx.2012.1030
Published online Oct. 4, 2012

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Byers, L.A. et al. Cancer Discov.; published online Sept. 6, 2012;
Contact: John V. Heymach, The University of Texas MD Anderson Cancer Center, Houston, Texas
Contact: Lauren Averett Byers, same affiliation as above