Reversing the paradigm: protein kinase C as a tumor suppressor.
dc.contributor.author | Newton, A | |
dc.contributor.author | Brognard, John | |
dc.date.accessioned | 2017-04-19T16:43:27Z | |
dc.date.available | 2017-04-19T16:43:27Z | |
dc.date.issued | 2017-03-07 | |
dc.identifier.citation | Reversing the paradigm: protein kinase C as a tumor suppressor. 2017, Trends Pharmacol Sci | en |
dc.identifier.issn | 1873-3735 | |
dc.identifier.pmid | 28283201 | |
dc.identifier.doi | 10.1016/j.tips.2017.02.002 | |
dc.identifier.uri | http://hdl.handle.net/10541/620252 | |
dc.description.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. | |
dc.language.iso | en | en |
dc.rights | Archived with thanks to Trends in pharmacological sciences | en |
dc.title | Reversing the paradigm: protein kinase C as a tumor suppressor. | en |
dc.type | Article | en |
dc.contributor.department | Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093-0721, USA | en |
dc.identifier.journal | Trends in Pharmacological Sciences | en |
html.description.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. |