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The Cons of Chemotherapy

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In a video posted at Scientific American, Judith Campisi of the Buck Institute for Research on Aging explains that the damage chemotherapeutic agents do to cancer cells may actually contribute to future cancer development. Cellular senescence has long been established as an effective anti-tumor mechanism, because if the cells can't divide, they can't form tumors, Campisi says. However, she adds, it's not just a simple cell shutdown, but rather a "dramatic reprogramming in the pattern of gene expression." As she and her colleagues discovered a few years ago, one of those programming changes involves genes that code for proteins that were secreted outside the cell. This gave the researchers the idea that a senescent cell itself could drive phenotypes and diseases that are associated with aging, like cancer. They termed it the senescence-associated secretory phenotype, Campisi adds, and it is now known to be induced primarily by factors that damage the genome and the epigenome. And the DNA-damaging agents that are the basis for many cancer therapeutics certainly qualify.

In addition, Campisi says, many of the genes activated by this damage response code for proteins involved in inflammation, growth factors, factors that disrupt blood vessel growth, and proteins that interact with immune system, among others — the most important of which are those that cause inflammation, which is linked to many age-related diseases, including cancer.

The implications of this discovery are far-reaching, Campisi adds, and could affect how young cancer patients are treated. She and her colleagues are experimenting with mice to see how chemotherapy delivered early in life affects development and aging, as it adds to the body's burden of senescent cells. "In the long term," Campisi adds, "we're going to have to think very hard … of when to do surgery relative to when these DNA damaging chemotherapies are applied."

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