Cervical cancer survival rates may improve with therapy targeting senescent cells
Having unprotected sex can not only make you pregnant, but it can also give you STDs caused by HPV or the human papillomavirus. HPV is one of the common sexually transmitted viruses which is largely detected by regular Pap smears that can identify early precancerous changes. It can also be prevented by vaccines against HPV.
While the survival rates of the most common cancers have improved since the mid-1970s, cervical and endometrial cancer survival rates have not, according to the American Cancer Society. But now with the first evidence that targeting senescence is one way to improve the survival rates.
How well a woman with cervical cancer responds to treatment and survives, correlates with the level of 10 proteins in their blood that also are associated with a “zombie” cell state called senescence, Medical College of Georgia scientists report.
They 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.
Here’s what you need to know about the proteins associated with cervical cancer survival
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 secretory phenotypes or SASPs.
Additionally, they 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,” they write in the journal Cancers.
Cervical cancer can be improved by managing zombie cells
“We want to figure out how we can treat cervical cancer better than we do. Beyond stage and treatment modality, what other factors are playing a big role in determining which patients survive and how they respond to radiation therapy,” said Dr Jin-Xiong She, director of the MCG Center for Biotechnology and Genomic Medicine, Georgia Research Alliance Eminent Scholar in Genomic Medicine and the study’s corresponding author.
“The most important conclusion of our paper is you want to manage senescence to improve therapy for cervical cancer,” she says.
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, says Dr Sharad Purohit, a biochemist in the MCG Center for Biotechnology and Genomic Medicine and the study’s first author.
what did the results say?
The researchers looked at blood levels of a total of 19 proteins they had found secreted by cells in a pathological site like a precancerous or cancerous cervix, although why the proteins are made is a question they can’t yet answer, says Purohit. This type of “liquid biopsy” can enable regular monitoring without actually doing a tissue biopsy each time, She says of the approach gaining ground in the cancer field.
They found that levels of 10 of the proteins had an impact on cervical cancer survival in the women who were an average of 49-years-old. All 10 were associated with cellular senescence, either as the largely destructive and inflammatory SASPs themselves or involved in regulating SASPs.
While cancer cells more typically are associated with rapid reproduction that enables cancer’s growth, senescent cells cannot divide and reproduce. But She categorizes the proteins these senescent cancer cells are secreting as “bad stuff,” which 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,” She said.
In the patients included in the study, everyone with stage 2 and most with stage 3 cancer received both internal and external radiation; 86 patients with stage 3 only received external beam radiation. Whether patients with low SASP levels could benefit from brachytherapy should be further explored, but they found no clear benefit to them, She and his colleagues write.