Thursday, August 2, 2012
Figure 1. Pol I inhibition in cancer. Researchers from the Peter MacCallum Research Centre and Cylene Pharmaceuticals Inc.
have published data in Cancer Cell
showing that a small molecule inhibitor of RNA polymerase I (Pol I) reduced
growth of hematological cancers in mice.
lymphoma cells, the Pol I inhibitor CX-5461 blocked Pol I with low nanomolar
triggering a stress response involving the release of ribosomal proteins from
the nucleolus [b], a
subcompartment of the nucleus. The ribosomal proteins then blocked interactions
between p53 and the p53 inhibitory protein mdm2 p53 binding protein homolog (MDM2; HDM2) [c], which in turn activated p53 [d] and allowed it to upregulate expression
of proapoptotic genes, killing the cancer cells [e].
and Peter MacCallum plan to start a Phase I trial of CX-5461 to treat
hematological malignancies this year.