Targeting protein kinase C subtypes in pancreatic cancer.
Targeting protein kinase C subtypes in pancreatic cancer.
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DOI：
10.1586/14737140.2015.1003810
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发表时间：
2015-04
影响因子：
3.3
通讯作者：
Storz P
中科院分区：
文献类型：
--
作者：
Storz P
在临床前研究中，蛋白激酶 C (PKC) 酶与调节胰腺癌发生和进展的许多方面有关。然而，针对经典 PKC 异构体的化合物的临床 I 期或 II 期试验并未成功。最近的研究表明，主要是非典型和新型 PKC 酶调节胰腺癌的致癌信号通路。这两个亚组的成员汇聚了由突变 Kras、生长因子和炎症细胞因子诱导的信号传导。已经描述了开发 aPKC 和 nPKC 抑制剂的不同方法；新化合物包括变构抑制剂和阻断 ATP 结合的抑制剂。
In preclinical studies protein kinase C (PKC) enzymes have been implicated in regulating many aspects of pancreatic cancer development and progression. However, clinical phase I or phase II trials with compounds targeting classical PKC isoforms were not successful. Recent studies implicate that mainly atypical and novel PKC enzymes regulate oncogenic signaling pathways in pancreatic cancer. Members of these two subgroups converge signaling induced by mutant Kras, growth factors and inflammatory cytokines. Different approaches for development of inhibitors for aPKC and nPKC have been described; and new compounds include allosteric inhibitors and inhibitors that block ATP binding.