Chemotherapy Can Cause Premature Aging in Cancer Cells

Received wisdom about cancer holds that the only way to stop the disease is to kill the multiplying cells. Simply arresting cell division with drugs, scientists assumed, wouldn't work because the cells would eventually mend and resume proliferation. But new research, described in a report published yesterday in the early online edition of the Proceedings of the National Academy of Sciences, suggests that in fact many treated tumor cells that stop dividing do so permanently. The findings could point the way toward new anticancer drugs.

To assess the effects of chemotherapy on cancer cells that survive treatment, Igor Roninson of the University of Illinois and colleagues studied colon cancer cells that had been exposed to the drug doxorubicin. Surviving cells, the team found, look a lot like normal cells that have ceased growing as a result of old age, or senescence. Analyses of the molecular changes in the senescent cells revealed that the cells had activated a number of genes, about 10 of which can arrest cell growth. Some of these so-called tumor suppressor genes function in normal cells but turn off when the cell becomes cancerous. Drug-induced senescence appears to turn these genes back on, halting cell division.

Some drugs activate harmful genes, too, however. The treated colon cancer cells, for example, turned on genes known to stimulate the growth of surrounding cells. They also turned on the infamous p21 gene, which itself activates a number of genes linked to diseases associated with old age—Alzheimer's among them. Other research indicates that this is not always the case, however. Roninson thus asserts that it should be possible to develop anticancer drugs that activate growth inhibitors associated with senescence without also inducing the harmful side effects.