Ferroptosis

a new form of non-apoptotic

regulated cell death characterized by iron dependency and lipid peroxidation

is involved in many pathological conditions such as neurodegenerative diseases

heart ischemia/reperfusion injury

acute renal failure

and cancer. While metabolic dysfunctions can lead to excessive lipid peroxidation culminating in ferroptotic cell death

glutathione peroxidase 4 (GPX4) resides in the center of a network that functions to prevent lipid hydroperoxides from accumulation

thereby suppressing ferroptosis. Indeed

RSL3 and other small-molecule GPX4 inhibitors can induce ferroptosis in not only cultured cancer cells but also tumor xenografts implanted in mice. Similarly

erastin and other system Xc

−

inhibitors can deplete intracellular glutathione required for GPX4 function

leading to lipid peroxidation and ferroptosis. As therapy-resistant cancer cells are sensitive to GPX4-targeted therapeutic regimens

the agents capable of inducing ferroptosis hold great promises to improve current cancer therapy. This review will outline the molecular basis of ferroptosis

but focus on the strategies and the agents developed in recent years for therapeutic induction of ferroptosis. The potentials of these ferroptosis-inducing agents

which include system Xc

−

inhibitors

GPX4 inhibitors

and iron-based nanoparticles

in cancer therapy will be subsequently discussed.