Inducing and exploiting vulnerabilities for the treatment of liver cancer.

ABSTRACT: Liver cancer remains difficult to treat, owing to a paucity of drugs that target critical dependencies^1,2; broad-spectrum kinase inhibitors such as sorafenib provide only a modest benefit to patients with hepatocellular carcinoma³. The induction of senescence may represent a strategy for the treatment of cancer, especially when combined with a second drug that selectively eliminates senescent cancer cells (senolysis)^4,5. Here, using a kinome-focused genetic screen, we show that pharmacological inhibition of the DNA-replication kinase CDC7 induces senescence selectively in liver cancer cells with mutations in TP53. A follow-up chemical screen identified the antidepressant sertraline as an agent that kills hepatocellular carcinoma cells that have been rendere

SUBMITTER: Wang C 

PROVIDER: S-EPMC6858884 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature