The therapeutic role of targeting protein kinase C in solid and hematologic malignancies

Klaus Podar, Marc S Raab, Dharminder Chauhan, Kenneth C Anderson

Publikation: Beitrag in Fachzeitschrift (peer-reviewed)Artikel in Fachzeitschrift

53 Zitate (Scopus)

Abstract

The protein kinase C (PKC) family, the most prominent target of tumor-promoting phorbol esters, is functionally linked to cell differentiation, growth, survival, migration and tumorigenesis and so mediates tumor cell proliferation, survival, multidrug resistance, invasion, metastasis and tumor angiogenesis. Therefore, targeting PKC isozymes may represent an attractive target for novel anticancer therapies. Recent preclinical and clinical studies using the macrocyclic bisindolylmaleimide enzastaurin or the N-benzylstaurosporine midostaurin demonstrate promising activity of PKC inhibitors in a variety of tumors, including diffuse large B-cell lymphoma, multiple myeloma and Waldenstroem's macroglobulinemia. However, our knowledge of PKCs in tumorigenesis is still only partial and each PKC isoform may contribute to tumorigenesis in a distinct way. Specifically, PKC isoforms have vastly different roles, which vary depending on expression levels of organ and tissue distribution, cell type, intracellular localization, protein-protein and lipid-protein interactions and the biologic environment. Although PKC activation generally positively affects tumor cell growth, motility, invasion and metastasis, recent reports show that many PKCs can also have negative effects. Therefore, it is necessary to further dissect the relative contribution of PKC isozymes in the development and progression of specific tumors in order to identify therapeutic opportunities, using either PKC inhibitors or PKC activators.

OriginalspracheEnglisch
Seiten (von - bis)1693-1707
Seitenumfang15
FachzeitschriftExpert Opinion on Investigational Drugs
Jahrgang16
Ausgabenummer10
DOIs
PublikationsstatusVeröffentlicht - Okt. 2007
Extern publiziertJa

ASJC Scopus Sachgebiete

  • Pharmakologie (medizinische)
  • Pharmakologie

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