Altered regulation of apoptosis provides potential mechanism for chemotherapy resistance

There are two principal modes of action by which chemotherapy agents affect the cell: either direct blockage of a vital cellular process or induction of programmed cell death (apoptosis) (37). Recently, it has also been shown that some chemotherapy agents induce a permanent cell cycle arrest that resembles the replicative senescence seen in the aging of normal cells; this represents a more cytostatic rather than tumoricidal approach (3840). It is not clear to what extent the three are, separately or together, responsible for the cytotoxicity effects of chemotherapy; however, increasing data suggest that apoptosis is one of the principle tumoricidal mechanisms of response (41-44). It follows that interference with the apoptotic response to drug therapy provides a viable defense against the damaging effects of cancer therapies (45,46). As a result, over the past decade, increasing attention has focused on the development of new therapeutic targets that either singly or in conjunction with existing treatments promote apoptosis. To better understand the variety of mechanisms by which apoptosis can be positively or negatively regulated in cancer cells, we will review some of the key features of the apoptotic response to therapy.

0 0

Post a comment