Tumor Cell Autophagy as an Adaptive Response Mediating Resistance to Treatments Such as Antiangiogenic Therapy

Simplified scheme of nonselective versus selective autophagy, and how they might be affected in cancer cells by oncogenic pathways and therapy-induced stressors. Shown are regulators of nonselective and selective autophagy in tumor cells. Hypoxia, as occurs naturally in the tumor microenvironment or as stimulated by antiangiogenic therapy, upregulates both nonselective and selective autophagy, with mechanisms more clearly identified for the former. Radiation, another anticancer therapy, has been shown to upregulate factors mediating nonselective autophagy. Bec-1, Beclin-1; PHD2, prolyl hydroxylase domain-containing protein 2; ROS, reactive oxygen species.