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Resistance To Anti Cancer Therapeutics Targeting Receptor Tyrosine Kinases And Downstream Pathways
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Book Synopsis Resistance to Anti-Cancer Therapeutics Targeting Receptor Tyrosine Kinases and Downstream Pathways by : Yosef Yarden
Download or read book Resistance to Anti-Cancer Therapeutics Targeting Receptor Tyrosine Kinases and Downstream Pathways written by Yosef Yarden and published by Springer. This book was released on 2018-03-28 with total page 255 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume comprehensively covers the multiplicity and diversity of mechanisms underlying patient resistance to currently approved anti-cancer drugs, including tyrosine kinase inhibitors and monoclonal antibodies, blockers of growth factor receptors and their downstream pathways, which play essential functions in cancer progression. Each chapter will cover a specific group of targets and the cognate drugs, along with molecular modes of innate and evolving resistance.
Book Synopsis Extracellular Targeting of Cell Signaling in Cancer by : James W. Janetka
Download or read book Extracellular Targeting of Cell Signaling in Cancer written by James W. Janetka and published by John Wiley & Sons. This book was released on 2018-05-10 with total page 486 pages. Available in PDF, EPUB and Kindle. Book excerpt: International experts present innovative therapeutic strategies to treat cancer patients and prevent disease progression Extracellular Targeting of Cell Signaling in Cancer highlights innovative therapeutic strategies to treat cancer metastasis and prevent tumor progression. Currently, there are no drugs available to treat or prevent metastatic cancer other than non-selective, toxic chemotherapy. With contributions from an international panel of experts in the field, the book integrates diverse aspects of biochemistry, molecular biology, protein engineering, proteomics, cell biology, pharmacology, biophysics, structural biology, medicinal chemistry and drug development. A large class of proteins called kinases are enzymes required by cancer cells to grow, proliferate, and survive apoptosis (death) by the immune system. Two important kinases are MET and RON which are receptor tyrosine kinases (RTKs) that initiate cell signaling pathways outside the cell surface in response to extracellular ligands (growth factors.) Both kinases are oncogenes which are required by cancer cells to migrate away from the primary tumor, invade surrounding tissue and metastasize. MET and RON reside on both cancer cells and the support cells surrounding the tumor, called the microenvironment. MET and RON are activated by their particular ligands, the growth factors HGF and MSP, respectively. Blocking MET and RON kinase activation and downstream signaling is a promising therapeutic strategy for preventing tumor progression and metastasis. Written for cancer physicians and biologists as well as drug discovery and development teams in both industry and academia, this is the first book of its kind which explores novel approaches to inhibit MET and RON kinases other than traditional small molecule kinase inhibitors. These new strategies target key tumorigenic processes on the outside of the cell, such as growth factor activation by proteases. These unique strategies have promising potential as an improved alternative to kinase inhibitors, chemotherapy, or radiation treatment.
Book Synopsis Resistance to Tyrosine Kinase Inhibitors by : Daniele Focosi
Download or read book Resistance to Tyrosine Kinase Inhibitors written by Daniele Focosi and published by Springer. This book was released on 2016-11-07 with total page 194 pages. Available in PDF, EPUB and Kindle. Book excerpt: The volume will serve as a primer on tyrosine kinase signaling and its importance in cancer. The volume will first introduce the common denominators of small-molecule and antibody-derived inhibitors, as well as the general phenomenon of resistance. The volume will then detail resistance to the most commonly used classes of tyrosine kinase inhibitors, and will focus specific chapters on resistance to BCR-ABL1, FLT3, angiokinase family members, and ALK inhibitors.
Book Synopsis Protein Tyrosine Kinases by : Doriano Fabbro
Download or read book Protein Tyrosine Kinases written by Doriano Fabbro and published by Springer Science & Business Media. This book was released on 2006 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein tyrosine kinases as targets for cancer and other indications / Mark Pearson, Carlos Garcia-Echeverria, Doriano Fabbro -- Inhibitors of signaling interfaces: targeting Src homology 2 domains in drug discovery / Carlos Garcia-Echeverria -- PI 3-kinase inhibition: a target for therapeutic intervention / Peter M. Finan, Stephen G. Ward -- Src as a target for pharmaceutical intervention: potential and limitations / Mira Susa ... [et al.] -- Activated FLT3 receptor tyrosine kinase as a therapeutic target in leukemia / Blanca Scheijen, James D. Griffin -- JAK kinases in leukemias/lymphomas and multiple myeloma / Renate Burger, Martin Gramatzki -- Glivec (Gleevec, Imatinib, STI571): a targeted therapy for CML / Elisabeth Buchdunger, Renaud Capedeville -- Platelet-derived growth factor: normal function, role in disease, and applications of PDGF antagonists / Tobias Sjoblom ... [et al.] -- Structural biology of protein tyrosine kinases / Sandra W. Cowan-Jacob ... [et al.] -- Testing of signal transduction inhibitors in animal models of cancer / Terence O'Reilly, Robert Cozens -- Phosphoproteomics in drug discovery and development / Michel F. Moran.
Book Synopsis Drug Resistance in Cancer Cells by : Kapil Mehta
Download or read book Drug Resistance in Cancer Cells written by Kapil Mehta and published by Springer Science & Business Media. This book was released on 2009-06-12 with total page 372 pages. Available in PDF, EPUB and Kindle. Book excerpt: It was estimated that in 2008, 1,437,180 patients would receive a new cancer diagnosisand 565,650individualswould die of cancer (Jemal et al. 2008).Since the vast majority of patients dying of cancer will have had anticancer therapy, both c- ventional chemotherapy and novel targeted therapy, it can be concluded that these patients are dying with drug resistant cancer. The term multidrug resistance is also apt – in that these patients die after having undergone multiple rounds of different and structurally unrelated cancer therapies. However, for some, the concept of m- tidrug resistance is a worn out idea, stemming from disappointment with the drug resistancereversalstrategiesthatwerecarriedoutinthe1990susingpumpinhibitors to block drug resistance mediated by P-glycoprotein, product of the MDR-1 gene. However, if one takes the larger de?nition – multidrug resistance as simultaneous resistance to multiple structurally unrelated anticancer therapies – its existence c- not be denied. The purpose of this book is to explore new concepts related to drug resistance in cancer, including resistance to the new molecularly targeted agents. Perhaps new terminology is needed for resistance that occurs following therapy with the targeted agents: Novel Targeted Agent Resistance (NTR). Alternatively, we can return to the original de?nition of multidrug resistance as simply the res- tance to multipleagents that occurs in the course of normalcancer progression.This resistance is likely to be mediated by many factors.
Book Synopsis Systems Modeling of Quantitative Kinetic Data Identifies Receptor Tyrosine Kinase-specific Resistance Mechanisms to MAPK Pathway Inhibition in Cancer by : Allison Claas
Download or read book Systems Modeling of Quantitative Kinetic Data Identifies Receptor Tyrosine Kinase-specific Resistance Mechanisms to MAPK Pathway Inhibition in Cancer written by Allison Claas and published by . This book was released on 2017 with total page 156 pages. Available in PDF, EPUB and Kindle. Book excerpt: Targeted cancer therapeutics have seen constraint in clinical efficacy due to resistance. Indicators for resistance may include genetic mutations or protein-level overexpression of targeted or bypass receptor tyrosine kinases (RTKs). While the latter is often attributed to gene amplification, genetic characterization of tumor biopsies has failed to explain substantial proportions of resistance. We hypothesize that post-synthesis mechanisms governing RTK levels may represent underappreciated contributors to drug resistance. We have developed an experimental and computational model for the simultaneous analysis of synthesis and post-synthesis mechanisms contributing to protein level changes. The experimental component quantitatively measures processes operating on multiple time scales in a multi-plexed fashion, with methods generalizable to any membrane bound protein. Parameter distribution estimation by fitting data to an integrative cellular model quantifies native RTK processes and enables the study of treatment induced mechanistic changes. It has been reported that triple negative breast cancer cell lines up-regulate many RTKs in response to Mek inhibition, although reported with conflicting mechanisms. Upon integrated analysis, we find both Axl and Her2 have increased lysate levels after Mek inhibition with 3 Mek inhibitors, Selumetinib, Binimetinib, and PD0325901. Axl changes are attributed to a decrease in proteolytic shedding and protein degradation, and Her2 changes are attributed to decreased synthesis. Met shows a decrease in proteolytic shedding similar to Axl, but compensating synthesis and degradation mechanisms counteract the effect. Contrastingly, Erk inhibition shows minor effects on RTK reprogramming, with Erk dimer inhibitor DEL-22379 exhibiting RTK specific protease effects and highlighting RTK specific outcomes of decreased endocytosis. This quantitative model enables prediction of combination therapies with mechanistic process inhibitors. Our predictions match experimental observations that Axl lysate level increases with Mek inhibition remains unchanged in the presence of transcriptional inhibition, supporting a role for post-synthesis mechanisms. Through additional combination with an Axl inhibitor, we are able to further the anti-proliferative and anti-migratory effect of Mek and transcriptional inhibition in TNBC. This study not only provides a novel and broadly applicable quantitative framework for characterizing RTK level changes, but also emphasizes the RTK, pathway target, and inhibitor variation of RTK reprogramming in drug resistance.
Book Synopsis Tyrosine Kinases as Druggable Targets in Cancer by : Huan Ren
Download or read book Tyrosine Kinases as Druggable Targets in Cancer written by Huan Ren and published by BoD – Books on Demand. This book was released on 2019-09-25 with total page 136 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein tyrosine kinase (PTK) deregulation contributes to growth of cancer and many other diseases. The development of small-molecule tyrosine kinase inhibitors (TKIs) that target the deregulated PTKs, such as epidermal growth factor receptor (EGFR) in non-small-cell lung cancer (NSCLC) and Bcr-ABL in chronic myeloid leukemia (CML), has revolutionized disease management. In this book, we examine a few aspects of PTKs and cancer, considering efficacy, predictive markers to therapeutic response, limitations, and future directions in TKI treatment. In this rapidly evolving field, overcoming therapeutic resistance is most challenging, and multi-targeting directs the next-generation TKIs and combination therapy as ongoing strategies in cancer treatment.
Book Synopsis Mechanisms of Drug Resistance in Cancer Therapy by : Mario Mandalà
Download or read book Mechanisms of Drug Resistance in Cancer Therapy written by Mario Mandalà and published by Springer. This book was released on 2019-01-10 with total page 297 pages. Available in PDF, EPUB and Kindle. Book excerpt: A major objective of this book is to reveal unprecedented opportunities to understand and overcome drug resistance through the clinical assessment of rational therapeutic drug combinations and the use of predictive and prognostic biomarkers to enable patient stratification and tailor treatments. It offers to the readers an updated overview on the possible reasons of failure of new and promising therapeutic opportunities.
Book Synopsis Role of Tyrosine Kinases in Gastrointestinal Malignancies by : Ganji Purnachandra Nagaraju
Download or read book Role of Tyrosine Kinases in Gastrointestinal Malignancies written by Ganji Purnachandra Nagaraju and published by Springer. This book was released on 2018-09-27 with total page 249 pages. Available in PDF, EPUB and Kindle. Book excerpt: The aim of this book is to provide comprehensive overview of the role of different tyrosine kinases in the progression and metastasis of various cancers of the gastrointestinal tract such as esophagus, liver, pancreas, stomach, and colorectal. Activation of various signaling pathways and tyrosine kinases are responsible for resistance to chemo and radiotherapy in these gastrointestinal malignancies. Targeting these tyrosine kinases, which regulate the activities of survival pathways in growth, and metastasis is a rational strategy in gastrointestinal cancer therapy. Each chapter embedded in this book covers information pertaining to a specific tyrosine kinase and its impact on various malignancies, which is not only significant for basic and clinical research investigations but will also be valued by students at advanced undergraduate to postgraduate levels.
Book Synopsis EGFR Signaling Networks in Cancer Therapy by : John D. Haley
Download or read book EGFR Signaling Networks in Cancer Therapy written by John D. Haley and published by Springer Science & Business Media. This book was released on 2009-03-01 with total page 393 pages. Available in PDF, EPUB and Kindle. Book excerpt: The epidermal gro wth factor (EGF ) receptor and its downstream signal transduction networks have been implicated in the ontology and maintenance of tumor tissues, which has motivated the discovery and development of molecularly targeted anti-EGF receptor therapies. Over decades of study, the EGF receptor structure, its ligand binding domains, the physical biochemistry underlying its intrinsic tyrosine kinase catalytic function and the modular interactions with SH2, PTB, and SH3 domain containing signaling adaptor p- teins required for signal transduction, have been extensively dissected. Not only is the EGF receptor the nexus of many streams of information, but it also forms one part of a calcul- ing device by forming dimers and oligomers with the other three receptors in its family in response to at least eleven ligands (some of which are expressed in multiple forms with overlapping or quite distinct functions). This phenomenon, while recruiting to the inner surface of the cell membrane and activating multiple second messenger proteins, also allows the possibility of cross talk between these systems, permitting a further layer of information to be exchanged. Less well described are the cross re gulation of the EGF receptor and other anti-apoptotic, mitogenic and metabolic signaling systems. The study of these systems has yielded new surprises. One hurdle in these efforts has been that signal transduction pathways have frequently been defined in the generic absence of their tissue-specific or cell-interaction specific context.
Download or read book Receptor Tyrosine Kinases written by and published by Academic Press. This book was released on 2020-06-24 with total page 446 pages. Available in PDF, EPUB and Kindle. Book excerpt: Receptor Tyrosine Kinases, Volume 147 in the Advances in Cancer Research series, provides invaluable information on the exciting and fast-moving field of cancer research in the area of Receptor Tyrosine Kinases (RTKs) in the context of major basic science and translational advances, their importance in the development of a large number of anti-cancer drugs over the decades, and a peek into postulated advances in the coming decades for a number of RTK. Chapters in this new release are contributed by a group of International leading scientists who have a rich history in this field. Provides the latest information on core advances in receptor tyrosine kinases in cancer research Offers outstanding and original reviews on a range of cancer research topics by leading authorities in the field Serves as an indispensable reference for faculty, researchers and students alike
Book Synopsis Multi-targeted Tyrosine Kinase Inhibitors in the Treatment of Cancer and Neurodegenerative Disorders by : Halilibrahim Ciftci
Download or read book Multi-targeted Tyrosine Kinase Inhibitors in the Treatment of Cancer and Neurodegenerative Disorders written by Halilibrahim Ciftci and published by Frontiers Media SA. This book was released on 2024-08-07 with total page 124 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tyrosine kinases, which catalyze the transfer of a phosphate from ATP to a hydroxyl group of a tyrosine residue, play a plethora of roles in the regulation of diverse functions in normal cells including cell growth, motility, differentiation, and metabolism. Moreover, they are also associated with oncogenesis. Tyrosine kinases are mainly classified as receptor tyrosine kinases and non-receptor tyrosine kinases, including crucial members. Epidermal growth factor receptor (EGFR) belongs to the ERBB family of receptor tyrosine kinases along with three other closely related receptors, namely HER-2, HER-3 and HER-4. EGFR and HER-2, lead to autophosphorylation of the intracellular domain through tyrosine kinase activity and subsequent stimulation of downstream cascade that may result in proliferation, suppression of apoptosis, metastasis and angiogenesis. On the other hand, c-Abl (Abl-1) is a non-receptor tyrosine kinase, which is also essential in the regulation of several antiapoptotic and proliferative signal transduction pathways. They have mainly been identified as important targets for several types of cancer such as EGFR for non-small-cell lung cancer, glioma and colorectal cancer, HER-2 for breast and colorectal cancers and Abl for chronic myeloid leukemia. One of the major platforms that they have participated in is neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis. Aberrant activity of tyrosine kinases, in particular EGFR and Abl, have been reported to induce apoptosis and cell cycle arrest in response to a wide range of stimuli resulting in neurodegeneration and neuroinflammation. The main goal of this Research Topic is to identify new and potent effective tyrosine kinase inhibitors to be effective in cancer and neurodegenerative disorders.
Book Synopsis Advances in Cancer Signal Transduction and Therapy by : Manoj K. Pandey
Download or read book Advances in Cancer Signal Transduction and Therapy written by Manoj K. Pandey and published by Bentham Science Publishers. This book was released on 2020-10-05 with total page 207 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer is driven by numerous genetic and epigenetic changes occurring at the cellular level. These changes drive normal cells to proliferate and escape processes that usually regulate their survival and migration. Many of these alterations are often associated with signaling pathways which regulate cell growth and division, cell death, survival, invasion and metastasis, and angiogenesis. Almost all cancer cells show high expression of signaling components including growth factor receptor tyrosine kinases (RTKs), small GTPases, serine/threonine kinases, cytoplasmic tyrosine kinases, lipid kinases, estrogen receptor, activation of transcription factors Myc and NF-κB, etc. Updated knowledge about these signaling components is highly desirable for researchers involved in developing therapies against cancer. Signal Transduction Research for Cancer Therapy covers advancements in research on the signaling pathways in the human body, especially in some types of cancers, such as breast cancer, pancreatic cancer and colon cancer. Key features of this volume include 8 focused topical reviews on signaling pathways in a specific cancer type, coverage of multiple cancer types (breast cancer, colon cancer, hepatocellular cancer, multiple myeloma, acute myeloid leukemia, and pancreatic cancer), and coverage of a wide array of signaling pathways (both receptor mediated and non receptor mediated pathways). This volume is essential reading for researchers in pharmaceutical R&D and postgraduate research programs in pharmacology and allied disciplines. Clinicians involved in oncology will also benefit from the information provided in the chapters. [Series Intro] This series provides scientists and clinicians with updated clinical information about signal transduction that will be valuable in their pursuit to investigate, develop, and apply novel agents to prevent or treat life-threatening diseases such as cancer. Contributions to the series will focus on methods that also enhance the quality of life for patients.
Book Synopsis Protein Kinase Inhibitors as Sensitizing Agents for Chemotherapy by :
Download or read book Protein Kinase Inhibitors as Sensitizing Agents for Chemotherapy written by and published by Academic Press. This book was released on 2018-11-21 with total page 294 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tyrosine Kinase Inhibitors as Sensitizing Agents for Chemotherapy, the fourth volume in the Cancer Sensitizing Agents for Chemotherapy Series, focuses on strategic combination therapies that involve a variety of tyrosine kinase inhibitors working together to overcome multi-drug resistance in cancer cells. The book discusses several tyrosine kinase inhibitors that have been used as sensitizing agents, such as EGFR, BCR-ABL, ALK and BRAF. In each chapter, readers will find comprehensive knowledge on the inhibitor and its action, including its biochemical, genetic, and molecular mechanisms' emphases. This book is a valuable source for oncologists, cancer researchers and those interested in applying new sensitizing agents to their research in clinical practice and in trials. Summarizes the sensitizing role of some tyrosine kinase inhibitors in existing research Brings recent findings in several cancer types, both experimental and clinically, with a particular emphases on underlying biochemical, genetic, and molecular mechanisms Provides an updated and comprehensive knowledge regarding the field of combinational cancer treatment
Book Synopsis Targeting the Receptor Tyrosine Kinase AXL in Cancer by : Nellie McDaniel
Download or read book Targeting the Receptor Tyrosine Kinase AXL in Cancer written by Nellie McDaniel and published by . This book was released on 2020 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: AXL is a receptor tyrosine kinase that has emerged as a promising target in a variety of cancers. The purpose of this work was to investigate the role of AXL in cancer and therapeutic resistance and to discover how to best abrogate the signaling of AXL. AXL is a member of the TAM family of receptor tyrosine kinases which have been shown to be involved in a variety of cancers and therapeutic responses. AXL specifically has been shown to mediate resistance to therapy in head and neck squamous cell carcinoma (HNSCC). Presented within is the discovery of a novel signaling axis between tyrosine 821 of AXL and c-ABL kinase that drives therapeutic resistance. Using preclinical models, we demonstrate that blockade of AXL is able to resensitize tumors to cetuximab and radiation treatment. Furthermore, inhibition of downstream signaling from AXL to c-ABL kinase is even more effective at overcoming resistance leading to tumor regression. This data provides rationale for clinical evaluation of therapeutics targeting AXL and c-ABL in the context of cetuximab- and/or radiation-resistant disease. Although targeting of AXL is potentially beneficial to overcome resistance and enhance current cancer therapies, resistance to AXL inhibition is inevitable. Presented within is the discovery of a novel mechanism of resistance to AXL-targeting mediated by the receptor tyrosine kinase MERTK. MERTK expression was increased after treatment with AXL-targeting agents but inhibition of MERTK sensitized HNSCC, triple-negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), and esophageal cancer preclinical models to AXL inhibition. Thus, co-targeting both AXL and MERTK would enhance the efficacy of AXL-targeting approaches and could be highly beneficial in a variety of cancer types.
Book Synopsis Protein Allostery in Drug Discovery by : Jian Zhang
Download or read book Protein Allostery in Drug Discovery written by Jian Zhang and published by Springer Nature. This book was released on 2019-11-09 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book focuses on protein allostery in drug discovery. Allosteric regulation, ʹthe second secret of lifeʹ, fine-tunes virtually most biological processes and controls physiological activities. Allostery can both cause human diseases and contribute to development of new therapeutics. Allosteric drugs exhibit unparalleled advantages compared to conventional orthosteric drugs, rendering the development of allosteric modulators as an appealing strategy to improve selectivity and pharmacodynamic properties in drug leads. The Series delineates the immense significance of protein allostery—as demonstrated by recent advances in the repertoires of the concept, its mechanistic mechanisms, and networks, characteristics of allosteric proteins, modulators, and sites, development of computational and experimental methods to predict allosteric sites, small-molecule allosteric modulators of protein kinases and G-protein coupled receptors, engineering allostery, and the underlying role of allostery in precise medicine. Comprehensive understanding of protein allostery is expected to guide the rational design of allosteric drugs for the treatment of human diseases. The book would be useful for scientists and students in the field of protein science and Pharmacology etc.
Book Synopsis Cancer Signaling by : Christoph Wagener
Download or read book Cancer Signaling written by Christoph Wagener and published by John Wiley & Sons. This book was released on 2016-08-12 with total page 357 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer, which has become the second-most prevalent health issue globally, is essentially a malfunction of cell signaling. Understanding how the intricate signaling networks of cells and tissues allow cancer to thrive - and how they can be turned into potent weapons against it - is the key to managing cancer in the clinic and improving the outcome of cancer therapies. In their ground-breaking textbook, the authors provide a compelling story of how cancer works on the molecular level, and how targeted therapies using kinase inhibitors and other modulators of signaling pathways can contain and eventually cure it. The first part of the book gives an introduction into the cell and molecular biology of cancer, focusing on the key mechanisms of cancer formation. The second part of the book introduces the main signaling transduction mechanisms responsible for carcinogenesis and compares their function in healthy versus cancer cells. In contrast to the complexity of its topic, the text is easy to read. 32 specially prepared teaching videos on key concepts and pathways in cancer signaling are available online for users of the print edition and have been integrated into the text in the enhanced e-book edition.
