PI3K/AKT/mTOR Signaling Network in Human Health and Diseases 3.0

Dear Colleagues,

We are happy to announce the third edition of “PI3K/AKT/mTOR Signaling Network in Human Health and Diseases”. The first edition resulted in 15 published papers, and the second edition resulted in 8 published papers.

The phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) signaling pathway plays a critical role in regulating cell growth, proliferation, survival, motility, differentiation, angiogenesis, and metabolism. Over the last two decades, major advances have been made in our molecular understanding of the role of PI3K/AKT/mTOR signaling in physiological processes, and we have discovered the complexity of the events mediated by this network, with the highly conserved mTOR complex (mTORC) as a central point of integration. In addition, increasing evidence suggests that PI3K/AKT/mTOR signaling is frequently dysregulated in diverse human pathologies, including malignant, neurodegenerative, autoimmune, cardiovascular, and metabolic diseases. Thus, therapeutic strategies with different rationales have been explored that target components of this signaling axis, as well as associated pathways that benefit patients in various clinical settings.

Rapalogs (e.g., temsirolimus and everolimus), which are first-generation mTOR inhibitors (mTORC1 inhibitors), have been used to treat advanced renal carcinoma and other tumors. Recently, second-generation mTOR inhibitors, called TOR kinase inhibitors (TORKIs), which compete with ATP within the catalytic site of mTOR and inhibit both mTORC1 and mTORC2, have undergone preclinical and clinical evaluation. These TORKIs are more potent than rapalogs in various preclinical cancer models, but show severe adverse effects in patients. In addition, several AKT and PI3K inhibitors have also been developed. In combination with PI3K or mTOR inhibitors, AKT inhibitors have shown promising preclinical results in several malignancies and other diseases. However, none of them have been approved by the U.S. FDA for treating human diseases.

Therefore, there is a dire need to advance the investigation of PI3K/AKT/mTOR signaling in human pathologies to develop novel therapies with high efficacy and low toxicity. This series of Special Issues, entitled “PI3K/AKT/mTOR Signaling Network in Human Health and Diseases 3.0”, aim to present a collection of articles related to the PI3K/AKT/mTOR signaling pathway in human health and diseases, including but not limited to cancer, aging, neurodegenerative disorders, inflammation, autoimmune diseases, obesity, and diabetes. Emphasis will be given to the molecular facets of PI3K/AKT/mTOR in specific diseases. Original research and review articles are welcome.

Dr. Jean Christopher Chamcheu
Dr. Claudia Bürger
Prof. Dr. Shile Huang
Guest Editors

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• PI3K/AKT/mTOR Signaling Network in Human Health and Diseases 2.0 in Cells (8 articles)