Salt-inducible kinases (SIKs) belong to AMP-activated protein kinase (AMPK) family, and functions mainly involve in regulating energy response-related physiological processes, such as gluconeogenesis and lipid metabolism. However, compared with another well-established energy-response kinase AMPK, SIK roles in human diseases, especially in diabetes and tumorigenesis, are rarely investigated. Recently, the pilot roles of SIKs in tumorigenesis have begun to attract more attention due to the finding that the tumor suppressor role of LKB1 in non-small-cell lung cancers (NSCLCs) is unexpectedly mediated by the SIK but not AMPK kinases. Thus, here we tend to comprehensively summarize the emerging upstream regulators, downstream substrates, mouse models, clinical relevance, and candidate inhibitors for SIKs, and shed light on SIKs as the potential therapeutic targets for cancer therapies.
In recent years, the incidence rate of breast cancer has increased year by year, and it has become a major threat to the health of women globally. Among all breast cancer subtypes, the hormone receptor (HR) + /human epidermal growth factor receptor 2 (HER2)luminal subtype breast cancer is the most common form of breast cancer. cyclin-dependent kinase 4 and 6 (cdK4/6) inhibitors, the hotspots in the field of targeted therapy for breast cancer, have proved to exhibit a good effect on patients with HR + /HER2breast cancer in a number of clinical trials, but the problem of drug resistance is inevitable. At present, three specific cdK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) have been approved by the USA Food and Drug Administration for the first-line treatment of HR + /HER2breast cancer. The drug resistance mechanisms of cdK4/6 inhibitors can be divided into cell cycle-specific resistance and cell cycle non-specific resistance. With the discovery of the drug resistance mechanism of cdK4/6 inhibitors, various targeted strategies have been proposed. The present review mainly discusses the mechanism of cdK4/6 inhibitors, drug resistance mechanisms and treatment strategies after resistance.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.