WIP1 phosphatase as pharmacological target in cancer therapy.
DNA damage response (DDR) pathway protects cells from genome instability and prevents cancer development. Tumor suppressor p53 is a key molecule that interconnects DDR, cell cycle checkpoints, and cell fate decisions in the presence of genotoxic stress. Inactivating mutations in TP53 and other genes implicated in DDR potentiate cancer development and also influence the sensitivity of cancer cells to treatment. Protein phosphatase 2C delta (referred to as WIP1) is a negative regulator of DDR and has been proposed as potential pharmaceutical target. Until recently, exploitation of WIP1 inhibition for suppression of cancer cell growth was compromised by the lack of selective small-molecule inhibitors effective at cellular and organismal levels. Here, we review recent advances in development of WIP1 inhibitors and discuss their potential use in cancer treatment.
['Pecháčková|Soňa|S|', 'Burdová|Kamila|K|', 'Macurek|Libor|L|0000-0002-0987-1238']
D000818:Animals D000970:Antineoplastic Agents D004249:DNA Damage D006801:Humans D009369:Neoplasms D009857:Oncogenes D011487:Protein Conformation D000071636:Protein Phosphatase 2C D016159:Tumor Suppressor Protein p53
Phosphatase Cancer DNA damage response p53 Checkpoint Inhibitor