Researchers at the Medical College of Georgia have identified a panel of biomarkers associated with cellular senescence—a dormant state that leads to cell cycle arrest in tumors—that can predict survival in cervical cancer patients. Published October 2020 in Cancers, the results could help identify patients that would benefit most from brachytherapy, an internal radiation treatment that targets the cervix.
Using a bead-based immunoassay, the researchers conducted a retrospective analysis of samples from 565 women with stage II or III cervical cancer, focusing on 19 serum proteins. Out of the 19 proteins, 10 were found to impact patient survival.
All 10 proteins were found to have a role in cellular senescence-associated secreted phenotype (SASP), either as SASP proteins (e.g. inflammatory cytokines and chemokines) or as part of its regulation. Research shows that SASP can turn senescent cells into pro-inflammatory cells that can promote tumor progression. In cervical cancer, human papillomavirus (HPV) infections cause inflammation, leading to SASP and contributing to the progression of cervical cancer.
The researchers found that patients with high expression of SASP proteins had poorer survival than those with low SASP.
Further analysis showed that brachytherapy improved outcomes in SASP-high patients, but not in SASP-low patients, suggesting that brachytherapy kills senescent cells, leading to better survival, while external radiotherapy does not, according to the study’s authors.
Overall, the authors write that their results suggest that treatments for cervical cancer that reduce senescence, such as senolytics, may help ameliorate survival rates—which have not improved in over thirty years.