Preclinical and clinical development of novel agents that target the protein kinase C family.
Protein kinase C (PKC) family comprises more than 12 serine-/threonine-specific isoenzymes. PKC isoenzymes play a complex role in the transduction of signal from tyrosine kinase receptor modulating proliferation, cell cycle, apoptosis, invasion, differentiation, and senescence in both cancer cells and endothelial cells. Thereby, inhibition and/or activation of specific PKCs is thought to control tumor growth by interacting directly with cancer cells and indirectly by blocking tumor angiogenesis. Furthermore, PKCs are known to modulate multi-drug resistance, providing a rational for the combination of PKCs modulators with classical cytotoxic drugs. During the past few years, preclinical and clinical data with first-generation PKC inhibitors/activators provided insight that PKCs may indeed represent attractive targets for the discovery of small molecules with new anticancer properties. In this review, we will provide an overview on the current understanding of PKC participation in chemotherapeutic resistance, the possible implications in cancer treatment, and the potential of most recent PKC inhibitors in molecular cancer therapeutics.
Serova
Maria
M
U716, Hopital Saint-Louis, Paris, France
Ghoul
Aïda
A
Benhadji
Karim A
KA
Cvitkovic
Esteban
E
Faivre
Sandrine
S
Calvo
Fabien
F
Lokiec
François
F
Raymond
Eric
E
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002986:Clinical Trials as Topic; D018432:Drug Resistance, Multiple / Q000502:physiology*; D015507:Drugs, Investigational; D006801:Humans; D007527:Isoenzymes; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C