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Driven by chronic overnutrition and associated with obesity, metabolic dysfunction-associated steatotic liver disease is increasing in prevalence. This Review discusses two main therapeutic approaches: improving the metabolism with incretin mimetics such as semaglutide and directly targeting the liver with agents such as the recently approved resmetirom.
Lysine acetylation is a post-translational modification on histones and other proteins that is catalysed by acetyltransferases (‘writers’) and mediates interactions with bromodomains and other ‘reader’ domains. This Review summarizes the properties and functions of these writers and readers and discusses efforts to identify small-molecule therapeutics that target them, some of which are being evaluated in clinical trials.
Recent progress in understanding senescence has spurred interest in the development of approaches that target senescent cells. This Review assesses the current status of senotherapies, such as senolytics and senomorphics, how these approaches can be combined with cancer therapies, and the challenges and opportunities in moving senotherapies to clinical practice.
Defects in the DNA damage response have been utilized therapeutically for cancer for a decade. This Review analyses the lessons learnt from the development of PARP inhibitors and how these may be applied to new targets to maximize success. Targeting multiple DNA damage response pathways simultaneously and combinations with other therapies are also discussed.
