Emerging roles of the p38 MAPK and PI3K/AKT/mTOR pathways in oncogene-induced senescence

• Recent advances in OIS mechanisms are discussed.
• The role of the p38 MAPK pathway in OIS is highlighted.
• The role of the PI3K/AKT/mTOR pathway in OIS is explored.

Oncogene-induced senescence (OIS) is a tumor-suppressing response that must be disrupted for cancer to develop. Mechanistic insights into OIS have begun to emerge. Activation of the p53/p21WAF1 and/or p16INK4A tumor-suppressor pathways is essential for OIS. Moreover, the DNA damage response, chromatin remodeling, and senescence-associated secretory phenotype (SASP) are important for the initiation and maintenance of OIS. This review discusses recent advances in elucidating the mechanisms of OIS, focusing on the roles of the p38 mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/cellular homolog of murine thymoma virus AKT/mammalian target of rapamycin (mTOR) pathways. These studies indicate that OIS is mediated by an intricate signaling network. Further delineation of this network may lead to development of new cancer therapies targeting OIS.