Biomarkers-guided precision therapeutics has revolutionized the clinical development and administration of molecular-targeted anticancer agents. Tailored precision cancer therapy exhibits better response rate compared to unselective treatment. Protein kinases have critical roles in cell signaling, metabolism, proliferation, survival and migration. Aberrant activation of protein kinases is critical for tumor growth and progression. Hence, protein kinases are key targets for molecular targeted cancer therapy. The serine/threonine kinase Akt is frequently activated in various types of cancer. Activation of Akt promotes tumor progression and drug resistance. Since the first Akt inhibitor was reported in 2000, many Akt inhibitors have been developed and evaluated in either early or late stage of clinical trials, which take advantage of liquid biopsy and genomic or molecular profiling to realize personalized cancer therapy. Two inhibitors, capivasertib and ipatasertib, are being tested in phase III clinical trials for cancer therapy. Here, we highlight recent progress of Akt signaling pathway, review the up-to-date data from clinical studies of Akt inhibitors and discuss the potential biomarkers that may help personalized treatment of cancer with Akt inhibitors. In addition, we also discuss how Akt may confer the vulnerability of cancer cells to some kinds of anticancer agents.
A series of commercially useful substituted heterocyclic ureas have been synthesised via selenium-catalysed reductive carbonylation of substituted nitrobenzezes with aminopyridine or aminopyrimidine derivatives as co-reagents and carbon monoxide as carbonylating reagent.
For China to reach its “dual carbon” aim, the digital economy presents both opportunities and obstacles. This paper examines the potential impact of digital economy development on regional carbon dioxide emissions, concluding that while the direct impact on regional carbon dioxide emissions through industrial structure upgrading and technological progress is unclear, the indirect impact through promoting energy structure transformation is both positive and clear. This research experimentally validates the results of a theoretical analysis using panel data from 30 Chinese provinces from 2011 to 2019 and the STIRPAT model and discovers an inverted U-shaped association between digital economy development and regional carbon dioxide emissions. According to the transmission path test, the digital economy primarily achieves its carbon dioxide emission reduction effect by promoting energy structure transformation, while the carbon dioxide emission reduction effect from upgrading industrial institutions and technological progress is insignificant. By region, the expansion of the digital economy in eastern China has a large carbon dioxide emission reduction effect but not in central and western China. The policy implication of this paper is that curbing new carbon dioxide emissions caused by digital infrastructure construction using the digital economy to accelerate energy structure transformation and accelerating digital economy development in central and western China can be effective policy options for the Chinese government to achieve the goal of carbon dioxide emission reduction.
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