Journal ArticleDOI
Targeting PI3K/AKT/mTOR network for treatment of leukemia.
Jessika Bertacchini,Nazanin Heidari,Laura Mediani,Silvano Capitani,Mohammad Shahjahani,Ahmad Ahmadzadeh,Najmaldin Saki +6 more
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TLDR
Modulation of miRNA can be used as a novel therapeutic approach to regulate the PI3K/Akt/mTOR pathway and may have pro-apoptotic and antiproliferative effects on hematological malignancies.Abstract:
Increased activity of PI3K/AKT/mTOR pathway has been observed in a huge number of malignancies. This pathway can function as a prosurvival factor in leukemia stem cells and early committed leukemic precursors and its inhibition is regarded as a therapeutic approach. Accordingly, the aim of this review is to evaluate the PI3K/Akt/mTOR inhibitors used in leukemia models. Inhibition of the PI3K/AKT/mTOR pathway has been reported to have beneficial therapeutic effects in leukemias, both in vitro in leukemia cell lines and in vivo in animal models. Overall, the use of dual PI3K/mTOR inhibitor, dual Akt/RTK inhibitor, Akt inhibitor, selective inhibitor of PI3K, mTOR inhibitor and dual PI3K/PDK1 inhibitor in CML, AML, APL, CLL, B-ALL and T-ALL has a better therapeutic effect than conventional treatments. Targeting the PI3K/Akt/mTOR pathway may have pro-apoptotic and antiproliferative effects on hematological malignancies. Furthermore, modulation of miRNA can be used as a novel therapeutic approach to regulate the PI3K/Akt/mTOR pathway. However, both aspects require further clinical studies.read more
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Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis
Hyun Sook Hwang,Hyun Ah Kim +1 more
TL;DR: Because current treatments for OA act only on symptoms and do not prevent or cure OA, chondrocyte apoptosis would be a valid target to modulate cartilage degeneration.
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Role of PI3K/AKT pathway in cancer: the framework of malignant behavior.
TL;DR: The current clinical trials of inhibitors against PI3K/AKT pathway in cancers found that the clinical efficacy of these inhibitors as monotherapy has so far been limited despite of the promising preclinical activity, which means combinations of targeted therapy may achieve better efficacies in cancers.
Journal ArticleDOI
Natural products targeting the PI3K-Akt-mTOR signaling pathway in cancer: A novel therapeutic strategy.
TL;DR: Various preclinical and clinical studies on bioactive compounds and constituents, which are derived from natural products, to target the PI3K-Akt-mTOR signaling pathway for cancer prevention and intervention are summarized and critically analyzed.
Journal ArticleDOI
Phosphatidylinositol 3-kinase/Akt signaling as a key mediator of tumor cell responsiveness to radiation.
TL;DR: The dysregulation of the components of upstream regulators of Akt as well as specific modifications ofAkt isoforms that enhance Akt activity are discussed and the mechanisms by which Akt interferes with repair of DNA after exposure to ionizing radiation, will be reviewed.
References
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Journal ArticleDOI
MicroRNA expression profiles classify human cancers
Jun Lu,Gad Getz,Eric A. Miska,Eric A. Miska,Ezequiel Alvarez-Saavedra,Justin Lamb,David Peck,Alejandro Sweet-Cordero,Alejandro Sweet-Cordero,Benjamin L. Ebert,Benjamin L. Ebert,Raymond H. Mak,Raymond H. Mak,Adolfo A. Ferrando,James R. Downing,Tyler Jacks,H. Robert Horvitz,H. Robert Horvitz,Todd R. Golub,Todd R. Golub,Todd R. Golub +20 more
TL;DR: A new, bead-based flow cytometric miRNA expression profiling method is used to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers, and finds the miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours.
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AKT/PKB signaling: navigating downstream.
TL;DR: Those Akt substrates that are most likely to contribute to the diverse cellular roles of Akt, which include cell survival, growth, proliferation, angiogenesis, metabolism, and migration are discussed.
Journal ArticleDOI
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
TL;DR: It is shown that TSC1–TSC2 inhibits the p70 ribosomal protein S6 kinase 1 and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation) and these functions are mediated by inhibition of the mammalian target of rapamycin (mTOR).
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Targeting the phosphoinositide 3-kinase pathway in cancer.
TL;DR: The potential of and challenges for the development of therapeutic agents that target this pathway in cancer are discussed and the potential and challenges in understanding of the PI3K pathway are highlighted.
Journal ArticleDOI
MicroRNAs in cancer.
TL;DR: In this paper, the effects of miRNA dysregulation in the cellular pathways that lead to the progressive conversion of normal cells into cancer cells and the potential to develop new molecular miRNA-targeted therapies are discussed.