Pro-senescence therapy for cancer: Time for the clinic

Abstract

Cellular senescence is a stable cell cycle arrest that occurs in diploid cells during aging. However, diploid cells can also experience an accelerated senescence response, termed pre-mature senescence, driven by DNA-damage, oncogene over-expression or loss of tumour suppressor genes. Recent evidences demonstrate that cellular senescence occurs also in tumours, where it opposes tumour initiation and progression. Senescence cells secrete a variety of cytokines and secreted factors, known as the senescence secretory phenotype (SASP), that regulate both the senescence entry and maintenance and can propagate senescence to adjacent cells, acting in a cell non-autonomous manner. In addition, SASP can also promote the recruitment and activation of immune cells that in turn mediate the clearance of senescent cancer cells. Several novel strategies have been developed to promote senescence in tumours. This approach has been named pro-senescence therapy for cancer. Among the most promising pro-senescence therapies for cancer there are compounds that can enhance or reactivate p53 in tumours, that blocks the cell cycle machinery and inhibit telomerase. These compounds are currently in both pre-clinical and clinical trials. In addition, SASP reprogramming or induction of PTEN-induced cellular senescence have recently been proposed as a promising therapeutic approach for the treatment of certain types of tumours. In conclusion, many essential proves of the biological relevance of senescence in cancer have been currently discovered and strategies aimed to identify novel pro-senescence compounds would aid the development of more efficient treatment modalities for cancer therapy.