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. 2020 Jun 15;6:51. doi: 10.1038/s41420-020-0286-z

Fig. 1. Schematic elucidating the mechanism of therapy-induced senescence.

Fig. 1

Activation of DNA damage response (DDR) pathways in response to therapy results in ATM/ATR kinase mediated induction of specific Cyclin dependent kinase inhibitors (CDKIs) that hinder the complex formation between cyclins and CDKs. Apart from DDRs, multiple signaling pathways (PI3K/AKT, Ras/MAPK, ROS/p38) are activated that converge on cell cycle checkpoints and the tumor suppressor Rb to induce senescence. Of note, certain agents can also activate the TGF-β signaling resulting in activation of cytokines (IL6, IL8) and Matrix metalloproteases (MMPs) culminating in senescence-associated secretory phenotype (SASP).