Greater Senescent Cell Burden Correlates with a Worse Cervical Cancer Survival Rate

It is thought that the burden of senescent cells is likely correlated with survival in many cancers. Senescent cells cease to replicate and begin to secrete pro-growth, pro-inflammation signals. Most senescent cells are rapidly destroyed by the immune system, but this process slows with age and thus senescent cells accumulate. Cellular senescence does act to suppress cancer in its earliest stages, by removing those cells most likely to become cancerous. Once a significant number of senescent cells are present, however, their signaling begins to aid cancer growth. Thus we might expect to see that the application of senolytic therapies, capable of selectively destroying senescent cells, will slow down the progression of cancer in many cases. The standard classes of cancer therapy, those that work by damaging cells quite aggressively, have the side-effect of inducing greater levels of cellular senescence throughout the body. They may all become more effective when paired with senolytics.

How well women with cervical cancer respond to treatment and survive correlates with the level of 10 proteins in their blood that also are associated with a cell state called senescence. Researchers looked at pretreatment levels of these proteins in the blood of 565 women with stage 2 and 3 cervical cancer, who received standard treatments of internal radiation, called brachytherapy, external radiation, or both. They found that women with low levels of the proteins secreted by senescent cells had higher survival rates than those with high levels of these senescence-associated secreted phenotypes, or SASPs.

Additionally researchers found that brachytherapy, which implants a radiation source close to the cervix, greatly improved survival of patients who had high levels of these SASPs but had little impact on those with low levels. "These results demonstrate that cellular senescence is a major determining factor for survival and therapeutic response in cervical cancer, and suggest that senescence reduction therapy may be an efficacious strategy to improve the therapeutic outcome of cervical cancer." In women with moderate to high blood levels of SASPs, use of a class of drugs called senolytics - which target these cells for elimination and are under study to improve age-related problems and disease - as an adjunct therapy could help.

While cancer cells more typically are associated with rapid reproduction that enables cancer's growth, senescent cells cannot divide and reproduce. The proteins these senescent cancer cells are secreting helps create an inflammatory state in which cancer thrives and helps lay the groundwork for cancer spread. It also provides some protection from radiation therapy, which like chemotherapy, works in part by killing off typically rapidly dividing cancer cells. "The senescent proteins really change how cancer cells may respond to therapy."

Link: https://jagwire.augusta.edu/cervical-cancer-survival-may-improve-by-targeting-senescent-zombie-cells/