Fig. 3.

A model for DSR in response to fasting. In a variety of normal cells, downstream elements of the IGF-I and other growth factors pathways, including the Akt, Ras and other proto-oncogenes, can be down-regulated in response to the reduction in growth factors caused by starvation. This down-regulation can block/reduce growth and promotes protection. By contrast, oncogenic mutations render tumor cells less responsive to fasting due to their constitutive pro-growth mode and relative independence from anti-growth signals. Constitutive activation of one of the pro-growth pathways may be sufficient for the continued growth. Therefore, cancer cells fail to or only partially respond to starvation conditions and continue to promote growth instead of entering a protected mode.