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mTOR Signaling Pathway and mTOR Inhibitors in Cancer Therapy

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TLDR
In this paper, dual PI3K/mTOR kinase inhibitors have been developed with the idea of overcoming resistance to the mTOR inhibition through preventing the activation of PI 3K/Akt as a result of release negative feedback loops.
Abstract
Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase. It is ubiquitously expressed in cells and is a therapeutic target for the cancer treatment arsenal. Despite the great responses obtained in tumors addicted to specific mutations or overactivation of key members of the mTOR pathway (HiF1α in RCC, cyclin D1 in MCL, or TSC in SEGA), mTOR inhibitors as single agents have modest activity. Dual PI3K/mTOR kinase inhibitors have been developed with the idea of overcoming resistance to the mTOR inhibition through preventing the activation of PI3K/Akt as a result of release negative feedback loops.

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Calorie Restriction and Dietary Restriction Mimetics: a Strategy for Improving Healthy Aging and Longevity.

TL;DR: Calorie restriction with adequate nutrition is the only non-genetic, and the most consistent non-pharmacological intervention that extends lifespan in model organisms from yeast to mammals, and protects against the deterioration of biological functions, delaying or reducing the risk of many age-related diseases.
Journal ArticleDOI

Autophagy in kidney disease and aging: lessons from rodent models

TL;DR: This review summarizes the recent advances in understanding the role of autophagy for kidney disease and aging and highlights the importance of knowing the carrier and removal status of canine coronavirus.
Journal ArticleDOI

mTOR Cross-Talk in Cancer and Potential for Combination Therapy

TL;DR: Together approaches are the most promising avenues to improve clinical efficacy of available therapeutics and overcome drug resistance in mTOR dysfunction, and prospects for mTOR inhibition as a therapeutic strategy are provided.
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Hypoxia Pathway Proteins As Central Mediators of Metabolism in the Tumor Cells and Their Microenvironment.

TL;DR: Current knowledge of the hypoxia-induced changes in metabolism during cancer development, how they are affected in the tumor cells and in the cells of the microenvironment are summarized, most prominently in immune cells.
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NVP-BEZ235, a novel dual PI3K/mTOR inhibitor, enhances the radiosensitivity of human glioma stem cells in vitro

TL;DR: NVP-BEZ235 increases the radiosensitivity of GSCs in vitro by activating autophagy that is associated with synergistic increase of apoptosis and cell-cycle arrest and decrease of DNA repair capacity.
References
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Journal ArticleDOI

Cancer statistics, 2010

TL;DR: The American Cancer Society as mentioned in this paper estimated the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data regarding cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from National Center for Health Statistics.
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Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib

TL;DR: A subgroup of patients with non-small-cell lung cancer have specific mutations in the EGFR gene which correlate with clinical responsiveness to the tyrosine kinase inhibitor gefitinib, and these mutations lead to increased growth factor signaling and confer susceptibility to the inhibitor.
PatentDOI

Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex

TL;DR: In this paper, the rictor-mTOR complex was used to identify compounds which modulate Akt activity mediated by the Rictor mTOR complex and methods for treating or preventing a disorder that is associated with aberrant Akt activation.
Journal ArticleDOI

One Hundred Years After “Carcinoid”: Epidemiology of and Prognostic Factors for Neuroendocrine Tumors in 35,825 Cases in the United States

TL;DR: Clinicians need to be become familiar with the natural history and patterns of disease progression, which are characteristic of these tumors, suggesting that NETs are more prevalent than previously reported.
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