The Pros and Cons of Targeting Protein Kinase c (PKC) in the Management of Cancer Patients

F.      Coluccio Leskow; M.      A. Krasnapolski; A.      J. Urtreger

Abstract

In the last years, PKC has become an attractive target for the treatment of cancer patients given its widely described role in carcinogenesis and tumor promotion. Despite the extensive research conducted on these phorbol ester receptors there is only limited knowledge about the contribution of each individual PKC isozyme in malignant transformation, mainly due to the different roles of each isozyme and their tissue-specificity. This diversity provides the unique opportunity to develop specific pharmacological agents, but the complex nature of the signaling pathways activated by different PKCs challenges selective drug therapies. Currently, several classes of PKC inhibitors including small molecule kinase inhibitors, biologic modulators, and anti-sense oligonucleotides are being evaluated for the treatment of different cancers where PKC isozymes were found to be deregulated as lung, colon, skin, prostate, and breast malignancies. In this article we will review which PKC isoforms are deregulated in different human cancers and summarize the mechanism of action of some of the major PKC modulators, analyzing the strengths and weaknesses of each one in the clinical setting.

Keywords: Cancer, clinical trials, PKC, tumor promotion, malignant transformation, specific pharmacological agents, anti-sense oligonucleotides, protein kinase C (PKC), therapeutic target, cell membrane receptors, several signaling cascades, cell cycle arrest, normal mammary cells, matrix metalloproteinases (MMP)