Promises and drawbacks of targeting cell cycle kinases in cancer.
The loss of ability in controlling cell cycle leads to aberrant cell growth and is a hallmark of cancer cells. Cell cycle regulation and progression mainly rely on protein phosphorylation events, therefore cell cycle kinases have long been viewed as potential targets for anticancer strategies. Consistently, cell cycle kinases are often dysregulated in different types of human cancer. Despite years of research and attempts directed at inhibiting cell cycle kinases, none of these approaches has been successfully translated to the clinic to halt tumorigenesis. Here, we review several currently pursued strategies and highlight both current challenges and some recent findings, which might help to develop new, better conceived therapeutic approaches based on cell-cycle kinase inhibition.
Pentimalli
Francesca
F
CROM Centro Ricerche Oncologiche Mercogliano, Avellino, 83013, Italy.
Giordano
Antonio
A
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D018844:Cyclin-Dependent Kinases