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 : 56. 33 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 : 80. 55 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 : 30. 50 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.​

Targeting Protein Kinases For Cancer Therapy

Author : David J. Matthews
ISBN : 9781118210772
Genre : Medical
File Size : 71. 82 MB
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An expert guide to targeting protein kinases in cancer therapy Research has shown that protein kinases can instigate the formation and spread of cancer when they transmit faulty signals inside cells. Because of this fact, pharmaceutical scientists have targeted kinases for intensive study, and have been working to develop medicinal roadblocks to sever their malignant means of communication. Complete with full-color presentations, Targeting Protein Kinases for Cancer Therapy defines the structural features of protein kinases and examines their cellular functions. Combining kinase biology with chemistry and pharmacology applications, this book enlists emerging data to drive the discovery of new cancer-fighting drugs. Valuable information includes: Comprehensive overviews of the major kinase families involved in oncology, integrating protein structure and function, and providing important tools to assist pharmaceutical researchers to understand and work in this dynamic area of cancer drug research Focus on small molecule inhibitors as well as other therapeutic modalities Discussion of kinase inhibitors that have entered clinical trials for the treatment of cancer, with an emphasis on molecules that have progressed to late stage clinical trials and, in a few cases, to market Providing a platform for further study, this important work reviews both the successes and challenges of kinase inhibitor therapy, and provides insight into future directions in the war against cancer.

Molecules To Medicine With Mtor

Author : Kenneth Maiese
ISBN : 9780128027554
Genre : Medical
File Size : 54. 2 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.

Targeting Pi3k Mtor Signaling In Cancer

Author : Alexandre Arcaro
ISBN : 9782889192441
Genre :
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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.

The Molecular Basis Of Cancer

Author : John Mendelsohn
ISBN : 9780323261968
Genre : Medical
File Size : 61. 50 MB
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Stay current with the latest discoveries in molecular and genomic research. Sweeping revisions throughout include eight brand-new chapters on: Tumor Suppressor Genes; Inflammation and Cancer; Cancer Systems Biology: The Future; Biomarkers Assessing Risk of Cancer; Understanding and Using Information About Cancer Genomes; The Technology of Analyzing Nucleic Acids in Cancer; Molecular Abnormalities in Kidney Cancer; and Molecular Pathology.

Molecular Approach To Cancer Management

Author : Gajanan V. Sherbet
ISBN : 9780128128978
Genre : Medical
File Size : 34. 57 MB
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Molecular Approach to Cancer Management discusses molecular mechanisms of cancer initiation, growth and secondary spread, emphasizing how this information can be used to devise new modes of treatment of cancer, especially in combatting secondary spread. The book addresses the basic concepts relating to cancer biology, the genetic determinants, and the signal transduction cascades associated with tumor growth, EMT, stem cell maintenance and propagation, and invasion and metastasis. The salient features of the signaling systems that are amenable to targeted manipulation are emphasized to facilitate research and development in the design of novel therapies and for the planning of new trials. This book is the only unique volume with coverage of topics that target therapy. As such, it is a valuable source for cancer researchers, molecular oncologists and members of the biomedical field who are interested in knowing more about molecular approaches to cancer therapy. Covers all relevant topics with a defined aim of targeted therapy Encompasses the basic aspects of cancer invasion and metastasis Discusses signaling systems operating in normal cells and their deregulation in cancer cells Directs attention to the foci in signaling systems that can be targeted with a new and conventional drug-based approach

The Oncogenomics Handbook

Author : William J. LaRochelle
ISBN : 9781592598939
Genre : Medical
File Size : 80. 86 MB
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An integrated overview of cancer drug discovery and development from the bench to the clinic, showing with broad strokes and representative examples the drug development process as a network of linked components leading from the discovered target to the ultimate therapeutic product. Following a systems biology approach, the authors explain genomic databases and how to discover oncological targets from them, how then to advance from the gene and transcript to the level of protein biochemistry, how next to move from the chemical realm to that of the living cell and, ultimately, pursue animal modeling and clinical development. Emerging cancer therapeutics including Ritux an, Erbitux, Gleevec Herceptin, Avastin, ABX-EGF, Velcade, Kepivance, Iressa, Tarceva, and Zevalin are addressed. Highlights include cancer genomics, pharmacogenomics, transcriptomics, gene expression analysis, proteomic and enzymatic cancer profiling technologies, and cellular and animal approaches to cancer target validation.

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

Author : Franco Muggia
ISBN : 9781455744084
Genre : Medical
File Size : 32. 12 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.

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