Figure 2: Overview of senescence pathways. Stimuli and cellular mechanisms responsible for the various stages of senescence. Each phase of senescence prevents cells from undergoing further cell division. M0 can occur through multiple mechanisms, and the relative contribution of each is a function of the factors driving mitogenic stimulation (e.g., BRAF versus HRAS mutation). M0 appears to be driven predominantly by the p16/Rb pathway in melanoma. a: Unfolded protein response (unique to HRAS mutant-positive cells).