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Reversing the paradigm: protein kinase C as a tumor suppressor.
Newton, A Brognard, John
Newton, A
Brognard, John
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Abstract
The discovery in the 1980s that protein kinase C (PKC) is a receptor for the tumor-promoting phorbol esters fueled the dogma that PKC is an oncoprotein. Yet 30+ years of clinical trials for cancer using PKC inhibitors not only failed, but in some instances worsened patient outcome. The recent analysis of cancer-associated mutations, from diverse cancers and throughout the PKC family, revealed that PKC isozymes are generally inactivated in cancer, supporting a tumor suppressive function. In keeping with a bona fide tumor suppressive role, germline causal loss-of-function (LOF) mutations in one isozyme have recently been identified in lymphoproliferative disorders. Thus, strategies in cancer treatment should focus on restoring rather than inhibiting PKC.
Authors
Newton, A
Brognard, John
Brognard, John
Description
Date
2017-03-07
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Article
Citation
Reversing the paradigm: protein kinase C as a tumor suppressor. 2017, Trends Pharmacol Sci