mTOR Inhibition for Cancer Therapy: Past, Present and Future

mTOR Inhibition for Cancer Therapy: Past, Present and Future
Author: Monica Mita
Publisher: Springer
Total Pages: 300
Release: 2015-11-18
Genre: Medical
ISBN: 2817804929

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.

Tumor Invasion and Metastasis

Tumor Invasion and Metastasis
Author: L.A. Liotta
Publisher: Springer Science & Business Media
Total Pages: 544
Release: 2012-12-06
Genre: Medical
ISBN: 9400975112

The clinical significance of tumor spread has always been appreciated. Yet, in spite of the pioneering work and outstanding contributions of investigators such as D. Coman, H. Green, B. Fisher, S. Wood and I. Zeidman, studies on metastasis rarely achieved the popularity afforded to more esoteric areas of tumor biology. Tumor dissemination, occurring as it does in a responding host and being composed of a series of dynamic int~ractions, is a highly complex phenomenon. Few investigators were brave enough to attempt to unravel the mechanisms involved. Paradoxically, this very complexity may have contributed, in part, to the recent upsurge of interest in metastasis research. More and more researchers are becoming fascinated by the complexities of the cellular interactions involved in tumor spread. Accompanying this intellectual stimulation have been technological advances in related fields which allow the derivation of new model systems. The mechanisms of metastatic spread are increasingly amenable to both the reductionist and holistic approaches and it is the purpose of this volume to present many of these model systems while emphasizing the intricacy and complexity of the processes they mimic. We have attempted to emphasize two topics not previously covered in depth in previous books on metastases. These are in vitro models of invasion and in teractions of tumor cells with connective tissue.

Molecules to Medicine with mTOR

Molecules to Medicine with mTOR
Author: Kenneth Maiese
Publisher: Academic Press
Total Pages: 474
Release: 2016-02-21
Genre: Science
ISBN: 012802755X

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.

The Heterogeneity of Cancer Metabolism

The Heterogeneity of Cancer Metabolism
Author: Anne Le
Publisher: Springer
Total Pages: 186
Release: 2018-06-26
Genre: Medical
ISBN: 331977736X

Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.

PI3K signalling

PI3K signalling
Author: Klaus Okkenhaug
Publisher: Frontiers Media SA
Total Pages: 140
Release: 2015-03-05
Genre: Immunologic diseases. Allergy
ISBN: 2889194191

The PI3Ks control many key functions in immune cells. PI3Ks phosphorylate PtdIns(4,5)P2 to yield PtdIns(3,4,5)P3. Initially, PI3K inhibitors such as Wortmannin, LY294002 and Rapamycin were used to establish a central role for Pi3K pathway in immune cells. Considerable progress in understanding the role of this pathway in cells of the immune system has been made in recent years, starting with analysis of various PI3K and Pten knockout mice and subsequently mTOR and Foxo knockout mice. Together, these experiments have revealed how PI3Ks control B cell and T cell development, T helper cell differentiation, regulatory T cell development and function, B cell and T cell trafficking, immunoglobulin class switching and much, much more. The PI3Kd inhibitor idelalisib has recently been approved for the treatment of B cell lymphoma. Clinical trials of other PI3K inhibitors in autoimmune and inflammatory diseases are also in progress. This is an opportune time to consider a Research Topic considering when what we have learned about the PI3K signalling module in lymphocyte biology and how this is making an impact on clinical immunology and haematology.

Killing Cancer

Killing Cancer
Author: Tuula Kallunki
Publisher: MDPI
Total Pages: 302
Release: 2020-11-17
Genre: Science
ISBN: 3039434403

Despite the efficiency of current cancer treatments, cancer is still a deadly disease for too many. In 2008, 7.6 million people died of cancer; with the current development, it is estimated that the annual cancer death number will grow to 13 million by 2030. There is clearly a need for not only more research but also more innovative and out of the mainstream scientific ideas to discover and develop even better cancer treatments. This book presents the collective works published in the recent Special Issue entitled “Killing Cancer: Discovery and Selection of New Target Molecules”. These articles comprise a selection of studies, ideas, and opinions that aim to facilitate knowledge, thoughts, and discussion about which biological and molecular mechanisms in cancer we should target and how we should target them.

mTOR Pathway and mTOR Inhibitors in Cancer Therapy

mTOR Pathway and mTOR Inhibitors in Cancer Therapy
Author: Vitaly A. Polunovsky
Publisher: Springer Science & Business Media
Total Pages: 307
Release: 2010-07-23
Genre: Medical
ISBN: 1603272712

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.

Metabolism in Cancer

Metabolism in Cancer
Author: Thorsten Cramer
Publisher: Springer
Total Pages: 272
Release: 2016-08-24
Genre: Medical
ISBN: 3319421182

This textbook presents concise chapters written by internationally respected experts on various important aspects of cancer-associated metabolism, offering a comprehensive overview of the central features of this exciting research field. The discovery that tumor cells display characteristic alterations of metabolic pathways has significantly changed our understanding of cancer: while the first description of tumor-specific changes in cellular energetics was published more than 90 years ago, the causal significance of this observation for the pathogenesis of cancer was only discovered in the post-genome era. The first 10 years of the twenty-first century were characterized by rapid advances in our grasp of the functional role of cancer-specific metabolism as well as the underlying molecular pathways. Various unanticipated interrelations between metabolic alterations and cancer-driving pathways were identified and currently await translation into diagnostic and therapeutic applications. Yet the speed, quantity, and complexity of these new discoveries make it difficult for researchers to keep up to date with the latest developments, an issue this book helps to remedy.

Targeted Therapies in Breast Cancer

Targeted Therapies in Breast Cancer
Author: Gw Sledge
Publisher: Clinical Pub
Total Pages: 0
Release: 2012-06
Genre: Breast
ISBN: 9781846920660

This new volume updates the reader on selected areas of targeted therapy in breast cancer, with special emphasis on chemoprevention strategies, drug resistance, biomarkers, combination chemotherapy, angiogenesis inhibition and pharmacogenomics in the context of clinical efficacy. This selected review of targeted therapies will guide the reader on effective treatment as part of an integrated programme of patient management.

Synthesis of Best-Seller Drugs

Synthesis of Best-Seller Drugs
Author: Ruben Vardanyan
Publisher: Academic Press
Total Pages: 870
Release: 2016-01-07
Genre: Medical
ISBN: 0124115241

Synthesis of Best-Seller Drugs is a key reference guide for all those involved with the design, development, and use of the best-selling drugs. Designed for ease of use, this book provides detailed information on the most popular drugs, using a practical layout arranged according to drug type. Each chapter reviews the main drugs in each of nearly 40 key therapeutic areas, also examining their classification, novel structural features, models of action, and synthesis. Of high interest to all those who work in the captivating areas of biologically active compounds and medicinal drug synthesis, in particular medicinal chemists, biochemists, and pharmacologists, the book aims to support current research efforts, while also encouraging future developments in this important field. - Describes methods of synthesis, bioactivity and related drugs in key therapeutic areas - Reviews the main drugs in each of nearly 40 key therapeutic areas, also examining their classification, novel structural features, models of action, and more - Presents a practical layout designed for use as a quick reference tool by those working in drug design, development and implementation