chemotherapy drugs on IV pole
Chemo drugs: side effects can persist for months
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By Jessica Hamzelou
Pain, nausea and utter exhaustion are just a few of the horrendous side effects most people experience when undergoing chemotherapy to treat cancer. Evidence is building that these effects are caused by a type of cell, and researchers have used a drug that targets these to stop side effects in mice.
When older cells naturally stop dividing, they become “senescent”. These kinds of cells also pump out a slew of chemicals that cause inflammation, which can damage surrounding tissue. Senescent cells have been linked to a growing list of age-related diseases, including Alzheimer’s, osteoporosis and heart failure.
Marco Demaria at the University of Groningen in the Netherlands wondered if senescence might be responsible for the long list of side effects associated with chemotherapy. “Most people have fatigue, and most of the time this becomes chronic,” he says. “Some people have muscle weakness, nausea, dizziness, problems with their bones or heart damage for example.” Such side effects can occur for months after treatment has finished.
To explore the effects of senescent cells, Demaria and his colleagues genetically engineered mice so these cells would fluoresce. They then gave the mice cancer, and one of four common chemotherapy drugs: doxorubicin, cisplatin, paclitaxel and temozolomide.
Chemotherapy increased the number of senescent cells in the mice. “We saw senescence everywhere: in the liver, lung, heart, skin and fat,” says Demaria.
The mice also started showing some typical chemo side effects, becoming less active and developing problems with their hearts and bone marrow, for instance.
In another experiment, the team gave some mice a drug known to kill senescent cells, a week after they had received chemotherapy. Their side effects were alleviated: these mice were more active and they didn’t develop any of the health problems the other mice had. These animals were also less likely to have their cancer return later on.
“We are able to interfere with multiple side effects at the same time,” says Demaria.
Next, the team looked at blood cells from women with breast cancer. They found that women with higher levels of senescent cells in their blood before starting chemotherapy had more severe side effects when their treatment began.
“It’s really interesting,” says Darren Baker at the Mayo Clinic in Rochester, Minnesota. “Chemotherapeutics are obviously good, but they really do have caustic side effects.”
Just as it had with the mice, wiping out senescent cells might help protect people from these unpleasant effects. The idea would be to administer such a drug once a person’s cancer has been cleared from the body through chemo. “If you have senescent cells, it’s a good idea to get rid of them as soon as you can,” says Baker.
“If we had a drug that we could use in humans, we could lower the toxicity and improve the efficacy of chemotherapy,” says Demaria. At the moment, there isn’t an appropriate drug that could be trialled in people. The drug given to the mice can cause a fatal shortage of blood platelets in humans.
But one potential compound is being developed to treat senescent cells in joint cartilage. This drug is being designed to break down as soon as it enters the bloodstream to avoid causing harmful effects elsewhere. It is set to enter clinical trials soon, says Baker.
Journal reference: Cancer Discovery, DOI: 10.1158/2159-8290.CD-16-0241
Read more: Secret to old-age health could lie in purging worn-out cells