Clearing Senescent Cells After Chemotherapy Treatment Helps Prevent Side Effects And Relapse

Chemotherapy is a lifeline for many cancer patients but comes with abundant side effects and increases senescent cell burden

Chemotherapy drugs work by preventing cellular division and they're highly effective. Not everyone responds well to treatment, but the introduction of chemotherapy has saved millions of lives and extended survival rates. Despite this, we're now realising such a treatment comes at a heavy short and long term cost, and paradoxically may increase cancer risk later in life. Aside from unpleasant side effects such as hair loss, we now know that chemotherapy's interference in cell division causes many cells to become senescent. As senescent cells are largely bad news and spew out inflammatory factors that raise body-wide inflammation and interfere with healthy function, removing these has emerged as one of the most promising longevity technologies so far. Indeed, now multiple companies are involved in senescent cell removal it seems likely to be the first real 'anti-aging' technology to be marketed. 

"While chemotherapy does save lives, it often comes with a very high price. Chemotherapy induces widespread senescence, contributing to persistent local and systemic inflammation. That’s why many patients feel so awful following treatment. Our work in mice studied the effects of chemotherapy on cancer relapse and other serious side effects. It provides a proof-of-principle that we hope can be translated into clinical practice”

Senescent cells have a distinctive appearance and behaviour

Tackling chemotherapy's burden

Senescent cells raise inflammation, which in turns raises cancer risk. Clearing these cells from the body has already shown striking health effects in mice, but aside from improving health in already 'healthy' individuals it could also help combat the collateral damage caused by rather brutal chemotherapy drugs. Now research at the Buck Institute has revealed that senescent cell removal does indeed counteract much of this damage in mice. 

What did the research find?

Using mice that had been genetically modified to allow easier senescent cell removal, the researchers treated mice with common chemotherapy drugs Doxorubicin, Paclitaxel, Temozolomide and Cisplatin.  They then demonstrated that eliminating these chemotherapy-induced senescent cells had a range of short and long term benefits. These included improving physical activity and strength while limiting bone marrow suppression, toxicity to the heart, cancer recurrence and metastasis. 

“Eliminating senescent cells was sufficient to almost entirely rescue the decline in physical activity in the treated mice. Normally, mice spend 40 percent of their time running. After chemotherapy that activity dropped to 10 percent. When we knocked out the senescent cells the mice returned to normal running"

When blood markers of senescence were monitored in women suffering from breast cancer, it was found that those with an increased senescent cell burden experienced the most fatigue following therapy. This suggests that senescence plays a critical role in health after treatment.

If we can develop an effective way of destroying these cells in humans, it could crucially prevent relapse later on and keep cancer risk down in the long term. We still have a lot of work to do, but it's an exciting finding and gives hope that cancer patients eventually won't have to deal with additional problems following already challenging treatment options. 

Read more at thebuck.org