mtor pathway and mtor inhibitors in cancer therapy cancer drug discovery and development

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Mtor Pathway And Mtor Inhibitors In Cancer Therapy

Author : Vitaly A. Polunovsky
ISBN : 1603272712
Genre : Medical
File Size : 45. 18 MB
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The main objective of this book is to provide an up-to-date survey of the rapidly advancing eld of cancer therapy. Moreover, since our knowledge in this area rapidly evolves, some data have got obsolete during the process of book editing. Our understanding of the mechanisms involved in cancer genesis and progression underwent unprecedented expansion during the last decade, opening a new era of cancer treatment – targeted therapy. The surge in this area results in no small part from studies conducted jointly by basic health scientists and clinical investigators. It is our hope that this book will help foster even further collaboration between investigators in these two disciplines. The target of rapamycin (TOR) was rst identi ed in Saccharomyces cerevisiae and subsequently in mammals (mTOR) as a conserved atypical serine/threonine kinase. In mammalian cells, mTOR exists in at least two multi-protein complexes that have critical roles in regulating cellular homeostasis and survival. As with many other areas of science, discovery of TOR signaling was fortuitous. Rapamycin was isolated as a product of the soil bacteria Streptomyces hygroscopicus, identi ed in a soil sample taken from the island of Rapa Nui (Easter Island). Rapamycin was rst discovered to be a potent antifungal agent and next as an immune suppressive drug. It was only later that it was found to be active as an antitumor agent in non-clinical models; although it was not developed for this indication. The history of rapamycin presents one of the rst examples of chemical genetics.

Mtor Inhibition For Cancer Therapy Past Present And Future

Author : Monica Mita
ISBN : 9782817804927
Genre : Medical
File Size : 27. 39 MB
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This book describes the challenges involved in developing mTOR inhibitors for cancer treatment, starting with an in-depth examination of their molecular mechanism of action, with emphasis on the class side-effects, efficacy and mechanisms of resistance, as well as on promising novel directions for their development, including novel compounds and rational combinations with other anti-neoplastic drugs. Over the last 10 years, inhibitors of mTOR have emerged as a major class of anticancer drugs. Two rapamycin analogs are currently approved for the treatment of renal cell carcinoma, and it is estimated that a variety of other tumor types could benefit from mTOR inhibition, with numerous clinical trials (including pivotal registration trials) already underway. Second-generation small-molecule inhibitors of the pathway have also shown promise in terms of their superior tolerability and efficacy and are undergoing extensive clinical evaluation, with an estimated 30+ compounds currently under evaluation.

Pi3k Mtor In Cancer And Cancer Therapy

Author : Nandini Dey
ISBN : 9783319342115
Genre : Medical
File Size : 68. 89 MB
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In the post human-genome project era, cancer specific genomic maps are redesigning tumor taxonomy by evolving from histopathology to molecular pathology. The success of a cancer drug today is fundamentally based on the success in identifying target genes that control beneficial pathways. The overwhelming power of genomics and proteomics has enlightened researchers about the fact that the PI3K-mTOR pathway is the most commonly up-regulated signal transduction pathway in various cancers, either by virtue of its activation downstream of many cell surface growth factor receptors or by virtue of its collateral and compensatory circuitry with RAS-MAPK pathway. Oncogenic signaling in the majority of solid tumors is sustained via the PI3K-AKT-mTOR pathway. Because of its prominent role in many cancer types, the PI3K-mTOR pathway has become a major therapeutic target. The volume includes two complementary parts which address the problem of etiology and disease progression and is intended to portray the very basic mechanisms of the PI3K-AKT-mTOR signaling pathway’s involvement in various facets of the cancer, including stem cell renewal, cell metabolism, angiogenesis, genetic instability, and drug resistance. Significant progress has been made in recent years elucidating the molecular mechanism of cancer cell proliferation, angiogenesis, and drug-resistance in relation to the PI3K-mTOR pathway and this volume provides an in-depth overview of recent developments made in this area.​

Tor

Author : George Thomas
ISBN : 9783642189302
Genre : Medical
File Size : 56. 94 MB
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TOR, the Target of Rapamycin was discovered a little over ten years ago in a genetic screen in S. cerevisiae in search of mutants resistant to the cytostatic effects of the antimycotic, rapamycin. Recent studies have placed TOR at the interface between nutrient sensing and the regulation of major anbolic and catabolic responses. The editors have gathered the leading figures in the field of TOR and its role in cellular homeostasis and human diseases.

Signalling Molecules As Targets In Cancer Therapy

Author : Vittorio de Franciscis
ISBN : 1600212433
Genre : Health & Fitness
File Size : 48. 10 MB
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This book presents state-of-the-art information on the molecules of cell signalling pathways that represent actual or future targets for cancer therapy. By giving an update of the most promising approaches in this rapidly evolving field, the book contributes to the translation of the recent advances in the knowledge of intracellular signalling into the generation of innovative biomolecules as specific tools to target the most promising tumour-specific candidates. The book begins logically with the molecules first encountered along the signalling pathways, the membrane receptors for growth factors (Part I). Next, Part II presents several examples of intracellular molecular targets that are situated one step beyond in the pathways, while Part III addresses the difficult task of tuning the delicate balance between cell death and survival. In Part IV, the reader is taken into the practical problems raised by the therapy of specific cancers (glioma, childhood leukaemia), and into an original strategy from the field of nuclear medicine with the potential to generate innovative molecular-targeted cancer therapies.

Enhancing Cancer Care

Author : Jennifer Barraclough
ISBN : 019929755X
Genre : Medical
File Size : 29. 87 MB
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A practical, evidence-based guide to complementary cancer therapies with an emphasis on enhancing practice; that is, using the therapies alongside conventional medicine, rather than as alternatives to it.

Targeting Pi3k Mtor Signaling In Cancer

Author : Alexandre Arcaro
ISBN : 9782889192441
Genre :
File Size : 87. 94 MB
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The phosphatidylinositol 3-kinase (PI3K)/mTOR pathway integrates signals from growth factors with nutrient signals and other conditions and controls multiple cell responses, including proliferation, survival and metabolism. Deregulation of the PI3K pathway has been extensively investigated in connection to cancer. Somatic or inherited mutations frequently occur in tumor suppressor genes (PTEN, TSC1/2, LKB1) and oncogenes (PIK3CA, PIK3R1, AKT) in the PI3K/mTOR pathway. The fact that the PI3K/mTOR pathway is deregulated in a large number of human malignancies, and its importance for different cellular responses, makes it an attractive drug target. Pharmacological PI3K inhibitors have played a very important role in studying cellular responses involving these enzymes. Currently, a wide range of selective PI3K inhibitors have been tested in preclinical studies and some have entered clinical trials in oncology. Rapamycin and its analogs targeting mTOR are effective in many preclinical cancer models. Although rapalogs are approved for the treatment of some cancers, their efficacy in clinical trials remains the subject of debate. Due to the complexity of the PI3K/mTOR signaling pathway, developing an effective anti-cancer therapy remains a challenge. The biggest challenge in curing cancer patients with various signaling pathway abnormalities is to target multiple components of different signal transduction pathways with mechanism-based combinatorial treatments.

Molecules To Medicine With Mtor

Author : Kenneth Maiese
ISBN : 9780128027554
Genre : Medical
File Size : 22. 85 MB
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Molecules to Medicine with mTOR: Translating Critical Pathways into Novel Therapeutic Strategies is a one-stop reference that thoroughly covers the mechanistic target of rapamycin (mTOR). mTOR, also known as the mammalian target of rapamycin, is a 289-kDa serine/threonine protein kinase that is ubiquitous throughout the body and has a critical role in gene transcription and protein formation, stem cell development, cell survival and senescence, aging, immunity, tissue regeneration and repair, metabolism, tumorigenesis, oxidative stress, and pathways of programmed cell death that include apoptosis and autophagy. Incorporating a translational medicine approach, this important reference highlights the basic cellular biology of mTOR pathways, presents the role of mTOR during normal physiologic function and disease, and illustrates how the mechanisms of mTOR can be targeted for current and future therapeutic treatment strategies. Coverage of mTOR signaling includes the entire life cycle of cells that impacts multiple systems of the body including those of nervous, cardiovascular, immune, musculoskeletal, endocrine, reproductive, renal, and respiratory origin. Covers the role of mTOR by internationally recognized expert contributors in the field. Provides a clear picture of the complexity of mTOR signaling as well as of the different approaches that could target this pathway at various levels. Includes analysis of the role of mTOR and in both health and disease. Serves as an important resource for a broad audience of healthcare providers, scientists, drug developers, and students in both clinical and research settings.

New Drugs For Malignancy An Issue Of Hematology Oncology Clinics Of North America E Book

Author : Franco Muggia
ISBN : 9781455744084
Genre : Medical
File Size : 66. 15 MB
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Topics include: Targeting IGF-1R, Tyrosine Kinase Inhibitors in Lung Cancer, Targeting mTOR, Targeting Hedgehog, Mitotic Inhibitors, Topoisomerase I Inhibitors , and New Strategies and Drugs Inhibiting Folate Pathways.

New Trends In Cancer For The 21st Century

Author : Antonio Llombart-Bosch
ISBN : 9781402051333
Genre : Medical
File Size : 44. 78 MB
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This volume contains the lectures held at the International Symposium on Cancer "New Trends in Cancer for the 21st Century". Fundamental researchers, politicians and representatives from patient coalitions share their knowledge and interests as well as their concerns and experiences. Not only do these papers provide state-of-the-art information on cancer, they are also an opportunity to look at the problem from different points of view.

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