Cell Cycle Inhibitor-Based Cancer Drugs

Cell cycle is a series of events making exact replicas of all their genetic material and resulting in two daughter cells with one complete copy of the entire genome. Both normal cell and tumor cell go through a growth cycle or cell cycle. However, normal cell and neoplastic cell differ in the number of cells that are in the various stages of cell cycle. It is thus possible to identify the tumor cell specific step during the cell cycle and inhibit the tumor cell growth, but spare the normal cells.

Table 7. Cell Cycle-Based Cancer Drugs

Torisel, Temsirolimus, an ester of the immunosuppressive agent sirolimus (Rapamune), is a novel mammalian target of rapamycin (mTOR) kinase inhibitor. It binds with high affinity to the immunophilin FKBP, and this complex inhibits mTOR kinase activity, which leads to G₁ to S phase cell cycle arrest. Temsirolimus has demonstrated significant inhibitory effects on tumor growth in both in vitro and in vivo models. It is an agent that is being developed to delay the time to tumor progression/recurrence and/or improve survival.

AP23573is a potent mTOR inhibitor that starves cancer cells and shrinks tumors by regulating the response of tumor cells to nutrients and growth factors and by controlling tumor blood supply and angiogenesis through effects on vascular endothelial growth factor in tumor and endothelial cells.

MKC-1 is an orally-active, small molecule, cell cycle inhibitor with a unique mechanism of action. Specifically, MKC-1 arrests cellular mitosis by inhibiting a novel intracellular target important in cellular trafficking that has been shown to be involved in cell division.