Senescent tumor cells: an overlooked adversary in the battle against cancer

• Published in: Experimental & molecular medicine 2021, 53(0), , pp.1-8
• Main Authors: Park, Soon Sang, Choi, Yong Won, Kim, Jang-Hee, Kim, Hong Seok, Park, Tae Jun
• Format: Article
• Language: English
• Subjects: 13/1; 13/106; 45/77; 45/91; 631/67/1059/2325; 631/67/327; 64/60; 82/51; 96/100; 96/21; Biomedical and Life Sciences; Biomedicine; Cancer; Carcinoma; Cell cycle; Cellular Senescence - genetics; Cytokines; Disease Management; Disease Susceptibility; Drug Development; Fibroblasts; Gene Expression Regulation; Humans; Immune clearance; Immunosuppressive agents; Invasiveness; Macrophages; Medical Biochemistry; Metastases; Molecular Medicine; Neoplasms - etiology; Neoplasms - metabolism; Neoplasms - pathology; Neoplasms - therapy; Organ Specificity - genetics; Phenotypes; Review; Review Article; Senescence; Senescence-Associated Secretory Phenotype - genetics; Stem Cells; Therapeutic targets; Tumor cells; Tumor Microenvironment; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/s12276-021-00717-5

Senescent cells in cancer tissue, including senescent fibroblasts and macrophages, have been reported to increase the malignant potency of cancer cells by secreting senescence-associated secretory phenotype (SASP). Otherwise, Senescence of tumor cells has been believed to inhibit tumor growth by halting the massive proliferation and increasing the chances of immune clearance. In particular, senescent tumor cells (STCs) have been thought that they rarely exist in carcinomas because oncogene-induced senescence needs to be overcome for protumorigenic cells to become malignant. However, recent studies have revealed that a considerable number of STCs are present in cancer tissue, even in metastatic sites. In fact, STCs are widely involved in cancer progression by leading to collective invasion and building a cytokine barrier to protect nonsenescent tumor cells from immune attack. Furthermore, therapy-induced STCs can induce tumor progression and recurrence by increasing stemness. However, obscure causative factors and their heterogeneity in various cancers make it difficult to establish the physiological role of STCs. Here, we summarize and review the current knowledge of the pathophysiology and role of STCs. We also outline the current status of therapeutic strategies for directly removing STCs or modulating the SASPs to maximize the positive functions of STCs while suppressing the negative functions. Cancer: Non-dividing tumor cells offer a promising therapeutic target Cancer cells that stop dividing but do not die help fuel tumor growth, and therapies that selectively eliminate or suppress these cells could reduce the risk of tumor recurrence and progression. A team from South Korea led by Hong Seok Kim from Inha University College of Medicine in Incheon and Tae Jun Park from Ajou University School of Medicine in Suwon review the cancer-promoting properties of tumor cells in irreversible cell cycle arrest, a state known as cellular senescence. They discuss how to identify these cells in cancer tissues and summarize the various drivers of senescence in the tumor microenvironment. Once established, the cells release local factors that both promote the invasiveness of nearby nonsenescent cancer cells and shield tumors from immune attack. Drugs that remove or modulate senescent tumor cells are now under investigation.