BioCentury
ARTICLE | Targets & Mechanisms

What to do with PKM2

January 17, 2013 8:00 AM UTC

Novartis AG researchers have shown that the absence of pyruvate kinase M2 isozyme has no effect on cancer cell proliferation in mice and suggest that inhibiting the enzyme alone might not be an effective strategy to stop tumor growth.1 The finding is surprising, given that knocking down the target is known to impair proliferation of cultured cancer cells. Biotechs working on modulators of the enzyme think it is too early to write off the target.

Pyruvate kinase occurs as two main isoforms-pyruvate kinase M1 isozyme (PKM1) is expressed in most normal cells as a constitutively active tetramer, whereas PKM2 is expressed in cancer cells either as a high-activity tetramer or a low-activity dimer. PKM2's oligomerization and activity is allosterically regulated by glycolysis intermediates...