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Ribonucleotide reductase M2 (RRM2; R2)

Cell culture and mouse studies identified RRM2 inhibitors that could help treat drug-resistant cancers. In cancer cell lines resistant to the ribonucleotide reductase inhibitors hydroxyurea and Gemzar gemcitabine, the lead RRM2 inhibitor decreased proliferation compared with hydroxyurea or gemcitabine alone. In mouse xenograft models of human ovarian cancer or leukemia, the inhibitor caused tumor regression. Next steps could include testing the inhibitor in additional cancer models.
Eli Lilly and Co. markets Gemzar to treat breast, ovarian, pancreatic and prostate cancers.
Sanofi markets the ribonucleotide reductase inhibitor Clolar clofarabine to treat acute lymphoblastic leukemia (ALL).
Calando Pharmaceuticals Inc.'s CALAA-01, a small interfering RNA duplex targeting the M2 subunit of RRM2 and delivered via the RNAi/oligonucleotide nanoparticle delivery (RONDEL) system, is in Phase I testing to treat solid tumors.

SciBX 6(42); doi:10.1038/scibx.2013.1184
Published online Oct. 31, 2013

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Zhou, B. et al. Cancer Res.;
published online Sept. 26, 2013;
Contact: Yun Yen, City of Hope, Duarte, Calif.