title: Senescent cells and their secretory phenotype as targets for cancer therapy.
abstract: Cancer is a devastating disease that increases exponentially with age. Cancer arises from cells that proliferate in an unregulated manner, an attribute that is countered by cellular senescence. Cellular senescence is a potent tumor-suppressive process that halts the proliferation, essentially irreversibly, of cells at risk for malignant transformation. A number of anti-cancer drugs have emerged that induce tumor cells to undergo cellular senescence. However, although a senescence response can halt the proliferation of cancer cells, the presence of senescent cells in tissues has been associated with age-related diseases, including, ironically, late-life cancer. Thus, anti-cancer therapies that can induce senescence might also drive aging phenotypes and age-related pathology. The deleterious effects of senescent cells most likely derive from their senescence-associated secretory phenotype or SASP. The SASP entails the secretion of numerous inflammatory cytokines, growth factors and proteases that can render the tissue microenvironment favorable for tumor growth. Here, we discuss the beneficial and detrimental effects of inducing cellular senescence, and propose strategies for targeting senescent cells as a means to fight cancer.
authors.affiliation: Buck Institute for Research on Aging, Novato, CA, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Velarde
authors.forename: Marco
authors.initials: M
authors.lastname: Demaria
authors.forename: Judith
authors.initials: J
authors.lastname: Campisi
mesh_terms: D000368:Aged; D016588:Anticarcinogenic Agents / Q000378:metabolism; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics; D002986:Clinical Trials as Topic; D003583:Cytokinins / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D016147:Genes, Tumor Suppressor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D010641:Phenotype; D049490:Systems Biology; D059016:Tumor Microenvironment / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016588:Anticarcinogenic Agents; D003583:Cytokinins; D036341:Intercellular Signaling Peptides and Proteins; D010447:Peptide Hydrolases