Figure 2.

Proposed senotherapeutic strategies: (a) anti-senescent agents may be especially useful against sorafenib resistance, a condition associated with senescent cell accumulation. Sorafenib induces the formation of senescent cells, in which it is no longer effective. Thus, a combination of sorafenib with an anti-senescent agent may result in better sorafenib response. (b) Pro-senescent agents may have the potential to halt tumor growth via inducing senescence. Thus, malignant cells enter proliferative arrest, and provided that the immune system works, most senescent cells are cleared in an immune-mediated fashion. (c) The combined “one-two punch” approach. In this treatment strategy, one starts with a pro-senescence agent, to promote senescence of malignant hepatocytes. As senescent cells may start to accumulate, an anti-senescent agent is administered in the next step, in order to enhance senescent cell clearance. Normal hepatocytes are presented in pale brown, malignant ones in dark brown, whereas senescent ones are presented in light blue with yellow outline.