Inhibition of PKC-βII for Chemoprevention

precancerous adenomaInappropriate activation of PKC isozymes has been implicated in many forms of cancer and researchers at the Mayo Clinic, Florida Campus, have been elucidating the roles of the isozymes in colon carcinoma using transgenic mice. Their earlier studies, reported in the January 15th issue of Cancer Research, demonstrated a requirement for PKC-βII in the initiation of colon cancer in mice exposed to a carcinogen. The same study also showed that PKC-ι/λ was required for cancer progression.

Now the scientists have shown that daily administration of the selective PKC-β inhibitor, Enzastaurin, provides a degree of protection to mice administered a carcinogen known to cause colon tumours. Since colon cancer develops over a 10-15 year period in humans, there is a large window of opportunity for the use of chemopreventative drugs. The authors suggest that Enzastaurin could represent a good candidate for clinical study in this setting because it has few side-effects.

enzastaurinEnzastaurin is currently in Phase III clinical trials for the treatment of B-cell lymphoma and high-grade brain gliomas. Although Enzastaurin is selective for PKC-β, it also significantly inhibits other PKC isozymes.

The full study with Enzastaurin is published in the February 15th issue of Cancer Research.