Cellular senescence in the tumor with a bone niche microenvironment: friend or foe?

Abstract

Cellular senescence is understood to be a biological process that is defined as irreversible growth arrest and was originally recognized as a tumor-suppressive mechanism that prevents further propagation of damaged cells. More recently, cellular senescence has been shown to have a dual role in prevention and tumor promotion. Senescent cells carry a senescence-associated secretory phenotype (SASP), which is altered by secretory factors including pro-inflammatory cytokines, chemokines, and other proteases, leading to the alteration of the tissue microenvironment. Though senescence would eventually halt the growth of cancerous potential cells, SASP contributes to the tumor environment by promoting inflammation, matrix remodeling, and tumor cell invasion. The paradox of tumor prevention/promotion is particularly relevant to the bone niche tumor microenvironment, where longer-lasting, chronic inflammation promotes tumor formation. Insights into a mechanistic understanding of cellular senescence and SASP provide the basis for targeted therapies, such as senolytics, which aim to eliminate senescent cells, or SASP inhibitors, which would eliminate the tumor-promoting effects of senescence. These therapeutic interventions offer significant clinical implications for treating cancer and healthy agin