LKB1 tumor suppressor: Therapeutic opportunities knock when LKB1 is inactivated

LKB1 is commonly thought of as a tumor suppressor gene because its hereditary mutation is responsible for a cancer syndrome,and somatic inactivation of LKB1 is found in nonsmall cell lung cancer,melanoma,and cervical cancers.However,unlike other tumor suppressors whose main function is to either suppress cell proliferation or promote cell death,one of the functions of LKB1-regulated AMPK signaling is to suppress cell proliferation in order to promote cell survival under energetic stress conditions.This unique,pro-survival function of LKB1 has led to the discovery of reagents,such as phenformin,that specifically exploit the vulnerability of LKB1-null cells in their defect in sensing energetic stress.Such targeted agents represent a novel treatment strategy because they induce cell killing when LKB1 is absent.This review article summarizes various vulnerabilities of LKB1-mutant cells that have been reported in the literature and discusses the potential of using existing or developing novel reagents to target cancer cells with defective LKB1.