Molecular mechanism regulating effect of anti-cancer agents

Faithful genome duplication is achieved by accurate coordination between DNA replication and chromosome segregation. Abnormalities occurring in this process are checked by biochemical signal transduction pathways, called checkpoints, which ensure the orderly progression of events in the cell cycle. Checkpoints prevent transition into subsequent phases until all processes in the previous phase are completed. Defects in cell cycle checkpoints result in gene mutations, chromosome damage, and aneuploidy, all of which contribute to tumorigenesis. However, it has recently been uncovered that the impairment of checkpoint function is the major reason why DNA damaging anti-cancer agents can selectively kill cancer cells. Given that G₁ and G₂ checkpoint functions are generally impaired in cancer cells, cells with DNA damage are unable to maintain G₂ arrest and eventually die as they enter mitosis. This process is known as mitotic catastrophe.