Monica Mita, Alain Mita, Eric K. Rowinsky's mTOR Inhibition for Cancer Therapy: Past, Present and Future PDF

By Monica Mita, Alain Mita, Eric K. Rowinsky

ISBN-10: 2817804910

ISBN-13: 9782817804910

ISBN-10: 2817804929

ISBN-13: 9782817804927

This ebook describes the demanding situations excited about constructing mTOR inhibitors for melanoma remedy, beginning with an in-depth exam in their molecular mechanism of motion, with emphasis at the type side-effects, efficacy and mechanisms of resistance, in addition to on promising novel instructions for his or her improvement, together with novel compounds and rational combos with different anti-neoplastic medicines.

Over the final 10 years, inhibitors of mTOR have emerged as an important category of anticancer medications. rapamycin analogs are at present authorized for the remedy of renal mobile carcinoma, and it's envisioned number of different tumor varieties may gain advantage from mTOR inhibition, with a variety of scientific trials (including pivotal registration trials) already underway. Second-generation small-molecule inhibitors of the pathway have additionally proven promise when it comes to their more desirable tolerability and efficacy and are present process huge medical review, with an anticipated 30+ compounds presently lower than review.

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BSTA promotes mTORC2-mediated phosphorylation of Akt1 to suppress expression of FoxC2 and stimulate adipocyte differentiation. Sci Signal. 2013;6(257):ra2. 176. Hung CM, et al. Rictor/mTORC2 loss in the Myf5 lineage reprograms brown fat metabolism and protects mice against obesity and metabolic disease. Cell Rep. 2014;8(1):256–71. 177. Philp A, Hamilton DL, Baar K. Signals mediating skeletal muscle remodeling by resistance exercise: PI3-kinase independent activation of mTORC1. ,2011;110(2):561–8.

EMBO J. 2003;22(12):3073–83. 7. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012;149(2):274–93. 8. Peterson TR, et al. DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell. 2009;137(5):873–86. 9. Kaizuka T, et al. Tti1 and Tel2 are critical factors in mammalian target of rapamycin complex assembly. J Biol Chem. 2010;285(26):20109–16. 10. Kim DH, et al. GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR.

164. Porstmann T, et al. SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth. Cell Metab. 2008;8(3):224–36. 165. Wang BT, et al. The mammalian target of rapamycin regulates cholesterol biosynthetic gene expression and exhibits a rapamycin-resistant transcriptional profile. Proc Natl Acad Sci U S A. 2011;108(37):15201–6. 2 The PI3K-mTOR Pathway 43 166. Peterson TR, et al. mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway. Cell. 2011;146(3):408–20.

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mTOR Inhibition for Cancer Therapy: Past, Present and Future by Monica Mita, Alain Mita, Eric K. Rowinsky


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