Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina.
Curr Pharm Biotechnol. 2011 Nov;12(11):1961-73. doi: 10.2174/138920111798376950.
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.
近年来，蛋白激酶 C（protein kinase C，PKC）已成为癌症治疗的一个有吸引力的靶点，因为其在致癌作用和肿瘤促进中具有广泛描述的作用。尽管已经对这些佛波酯受体进行了广泛的研究，但对于每种 PKC 同工酶在恶性转化中的贡献，人们的了解非常有限，主要是因为每种同工酶的作用不同及其组织特异性。这种多样性为开发特异性药理学制剂提供了独特的机会，但不同 PKC 激活的信号通路的复杂性对选择性药物治疗提出了挑战。目前，正在评估几类 PKC 抑制剂，包括小分子激酶抑制剂、生物调节剂和反义寡核苷酸，用于治疗 PKC 同工酶失调的不同癌症，如肺癌、结肠癌、皮肤癌、前列腺癌和乳腺癌。本文将综述不同人类癌症中哪些 PKC 同工酶失调，并总结一些主要 PKC 调节剂的作用机制，分析每种调节剂在临床环境中的优缺点。
