Molecular mechanism regulating effect of anti-cancer agents
Saya, H.
Gan to Kagaku Ryoho. Cancer and ChemoTherapy 36(1): 1-5
2009
ISSN/ISBN: 0385-0684 PMID: 19151557 Document Number: 630036
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.