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Pyruvate kinase M2 isozyme (PKM2); PKM1

Cell culture and mouse studies suggest targeting PKM2 may not be sufficient to inhibit tumor growth. Studies in mouse tumor xenograft models have previously shown that PKM2 is required for initial growth and establishment of tumors. In cultured colon carcinoma or adenocarcinoma cells, small hairpin RNA-mediated knockdown of PKM1 and PKM2, but not PKM1 or PKM2 alone, decreased pyruvate kinase activity and proliferation compared with no knockdown. However, in mouse xenograft models of established colon carcinoma or adenocarcinoma, individual or dual inhibition of PKM1 and PKM2 failed to decrease tumor growth. Next steps could include testing PKM2 modulators plus other antitumor compounds in mouse xenograft models to identify effective combination treatments.

SciBX 6(3); doi:10.1038/scibx.2013.54
Published online Jan. 24, 2013

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Cortés-Cros, M. et al. Proc. Natl. Acad. Sci. USA; published online Dec. 24, 2012;
Contact: Marta Cortés-Cros, Novartis Institutes for BioMedical Research, Basel, Switzerland