The role of protein kinase C-alpha (PKC-alpha) in melanoma.
In the 1980s, protein kinase C (PKC) was identified as a contributing factor in skin tumorigenesis. As drugs targeting specifically PKC have become available, the intent of this review was to assess the role of PKC, in particular of PKC-alpha in melanoma or other skin cancers. We reviewed and summarized published studies examining the role of PKC-alpha in the development of melanoma or other skin cancers. Most studies to date have been cell-culture based. In models of melanoma, PKC-alpha activation is typically associated with increased tumour cell proliferation, invasiveness and decreased differentiation, suggesting that PKC-alpha inhibitors, such as aprinocarsen, an antisense oligonucleotide directed against PKC-alpha, may be appropriate in the treatment of skin malignancies. Because of the recent developments on selective or specific PKC-alpha inhibitors, including aprinocarsen, there is a growing need to conduct further translational research, especially in melanoma patients, to identify the patient population that might benefit most from PKC-alpha targeted therapy.
Lahn
Michael M
MM
Divison of Oncology Product Development, Eli Lilly and Company, Indianapolis, IN 46285, USA. mlahn@lilly.com
Sundell
Karen L
KL
D000818:Animals; D006801:Humans; D008545:Melanoma / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D011493:Protein Kinase C / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D012878:Skin Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics / Q000628:therapy
C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha