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Author : Nour Al Abdullah Al Kafri
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (119 download)
Download or read book The Receptor Tyrosine Kinase Tyro3 as a Novel Drug Target in Cancer written by Nour Al Abdullah Al Kafri and published by . This book was released on 2020 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Author :
Publisher : Academic Press
ISBN 13 : 0128201835
Total Pages : 446 pages
Book Rating : 4.1/5 (282 download)
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
Author : Doriano Fabbro
Publisher : Springer Science & Business Media
ISBN 13 : 1592599621
Total Pages : 599 pages
Book Rating : 4.5/5 (925 download)
Download or read book Protein Tyrosine Kinases written by Doriano Fabbro and published by Springer Science & Business Media. This book was released on 2007-11-13 with total page 599 pages. Available in PDF, EPUB and Kindle. Book excerpt: Leading researchers, from the Novartis group that pioneered Gleevec/GlivecTM and around the world, comprehensively survey the state of the art in the drug discovery processes (bio- and chemoinformatics, structural biology, profiling, generation of resistance, etc.) aimed at generating PTK inhibitors for the treatment of various diseases, including cancer. Highlights include a discussion of the rationale and the progress made towards generating "selective" low molecular-weight kinase inhibitors; an analysis of the normal function, role in disease, and application of platelet-derived growth factor antagonists; and a summary of the factors involved in successful structure-based drug design. Additional chapters address the advantages and disadvantages of in vivo preclinical models for testing protein kinase inhibitors with antitumor activity and the utility of different methods in the drug discovery and development process for determining "on-target" vs "off-target" effects of kinase inhibitors.
Author : Huan Ren
Publisher : BoD – Books on Demand
ISBN 13 : 1789848083
Total Pages : 136 pages
Book Rating : 4.7/5 (898 download)
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.
Author : Deric L. Wheeler
Publisher : Springer
ISBN 13 : 3319118889
Total Pages : 888 pages
Book Rating : 4.3/5 (191 download)
Download or read book Receptor Tyrosine Kinases: Family and Subfamilies written by Deric L. Wheeler and published by Springer. This book was released on 2015-07-31 with total page 888 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book devotes a chapter to each RTK family and the multiple receptors within each family, thoroughly covering all of the RTKs. The chapters all follow the same structure, presenting this essential information in an accessible and user-friendly format. Each chapter covers one specific family of receptors and begins with a general introduction to that family and a comprehensive discussion of that receptor’s family in development and human disease. Following are in-depth analyses of each family’s receptors with discussions on the gene, protein, ligands, activation, and signaling pathways along with discussion of receptor processing and signal attenuation. Further, cross talk with other receptors systems, post-translational modification and specific unique characteristics to each RTK are discussed. Because it isolates and explains each family, this book is an essential companion volume to Receptor Tyrosine Kinases: Structure, Functions and Role in Human Disease, by the same authors, which talks about RTKs more generally and without the family-by-family detail.
Author : James W. Janetka
Publisher : John Wiley & Sons
ISBN 13 : 1119300207
Total Pages : 486 pages
Book Rating : 4.1/5 (193 download)
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.
Author : Deric L. Wheeler
Publisher : Springer
ISBN 13 : 1493920537
Total Pages : 452 pages
Book Rating : 4.4/5 (939 download)
Download or read book Receptor Tyrosine Kinases: Structure, Functions and Role in Human Disease written by Deric L. Wheeler and published by Springer. This book was released on 2014-11-26 with total page 452 pages. Available in PDF, EPUB and Kindle. Book excerpt: Receptor Tyrosine Kinase: Structure, Functions and Role in Human Disease, for the first time, systematically covers the shared structural and functional features of the RTK family. Receptor Tyrosine Kinases (RTKs) play critical roles in embryogenesis, normal physiology and several diseases. And over the last decade they have become the Number 1 targets of cancer drugs. To be able to conduct fundamental research or to attempt to develop pharmacological agents able to enhance or intercept them, it is essential first to understand the evolutionary origin of the 58 RTKs and their roles in invertebrates and in humans, as well as downstream signaling pathways. The assembly of chapters is written by experts and underscores commonalities between and among the RTKs. It is an ideal companion volume to The Receptor Tyrosine Kinase: Families and Subfamilies, which proceeds, family by family through all of the specific subfamilies of RTKs, along with their unique landmarks.
Author : Yosef Yarden
Publisher : Springer
ISBN 13 : 3319679325
Total Pages : 255 pages
Book Rating : 4.3/5 (196 download)
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.
Author : Nellie McDaniel
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (124 download)
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.
Author :
Publisher : Academic Press
ISBN 13 : 0128127384
Total Pages : 294 pages
Book Rating : 4.1/5 (281 download)
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
Author : Sylvie Eigeldinger-Berthou
Publisher :
ISBN 13 :
Total Pages : 148 pages
Book Rating : 4.:/5 (853 download)
Download or read book The Receptor Tyrosine Kinase Met in Cancer written by Sylvie Eigeldinger-Berthou and published by . This book was released on 2004 with total page 148 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Author : Afnan Abu-Thuraia
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (11 download)
Download or read book AXL Receptor Tyrosine Kinase in Breast Cancer written by Afnan Abu-Thuraia and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer is the most frequently diagnosed cancer in women where its progression to the metastatic stage poses a threat to the life of patients. The metastatic disease represents the central clinical challenge of solid tumor oncology such that mechanisms and pathways underlying the metastatic process must be better defined. The aberrant expression of the receptor tyrosine kinase (RTK) AXL has been linked clinically to metastasis and acquisition of drug resistance. AXL is a member of the TAM subfamily and functions in several biological processes such as dampening the immune response, clearing apoptotic cells and promoting cell survival. Despite its preferential upregulation in triple negative/basal B cell lines, studies have shown AXL expression in the clinic to be subtype independent. AXL can be activated by its ligand GAS6 or by a crosstalk with other RTKs. Upon its activation, AXL induces downstream signaling resulting in the activation of canonical signaling intermediates including MAPKs, AKT and PI 3-kinases. However, the specific signaling pathways engaged by AXL to confer such enhanced pro-invasion power are not known and the goal of this thesis is to identify AXL-specific substrates and downstream pathways that are behind AXL's significant role in maintaining an EMT state and reinforced mesenchymal phenotype in cancer cells. In search of upstream regulators of ELMO/DOCK1 complex involved in RAC activation, we reported ELMO scaffolds as direct substrates and binding partners of AXL. Through proteomics and mutagenesis approaches, we revealed phosphorylation of ELMO1/2 by AXL kinase on a conserved carboxyl-terminal tyrosine residue. In breast cancer cells, GAS6-dependent activation of AXL led to endogenous ELMO2 phosphorylation on Tyr-713 and AXL/ELMO complex formation. In addition, GAS6-induced RAC activation in breast cancer cells was dependent on ELMO2 expression and phosphorylation. Our work in chapter 2 defines a new mechanism by which AXL promotes cell proliferation and invasion and identifies inhibition of ELMO/DOCK pathway as a potential therapeutic target to stop AXL-induced metastases. While it still remains elusive how AXL signals to induce its pro-invasive phenotype, our work strove to identify specific substrates and signaling pathways that are significantly modulated upon AXL activation using a quantitative phosphoproteomics approach. By generating GAS6-induced AXL phosphoproteome, we found that AXL robustly modulates, among many different significant biological processes and pathways, the phosphorylation of a network of focal adhesion (FA) proteins culminating in faster FA disassembly. Interestingly, we found AXL modulation of FA pathway to be unique to AXL in comparison with other RTKs such as EGFR. NEDD9 FA protein was identified to be a direct substrate of AXL, where its phosphorylation modulates its complex formation with CRKII/DOCK3, and this subsequently orchestrates the AXL-mediated phosphorylation of the pseudo-kinase PEAK1. Our data revealed a distinct mechanism by which PEAK1 complexes with CSK kinase, mediating PXN phosphorylation and AXL-induced FA turnover. Using in vivo assays such as tail-vein metastasis assay and tumor growth assay, we revealed that gene inactivation of PEAK1 by CRISPR CAS9 decreased tumor growth and metastasis. Furthermore, our work in chapter 3 uncovers an unexpected and unique robust contribution of AXL signaling to FA dynamics revealing a long sought-after mechanism underlying AXL pro-invasive activity. This in-depth understanding of AXL regulated signaling networks identifies PEAK1 as a new therapeutic target in AXL positive tumors. In conclusion, this thesis identified, for the first time, AXL phosphoproteome and AXL specific downstream signaling pathways that may justify AXL's role as a promoter of metastasis and drug resistance. Our work reveals novel therapeutic drug targets that may hold a great potential if used in combinational therapeutics with AXL inhibition to prevent metastasis of AXL positive tumors.
Author : Christopher T. Cummings
Publisher :
ISBN 13 :
Total Pages : 107 pages
Book Rating : 4.:/5 (955 download)
Download or read book MERTK written by Christopher T. Cummings and published by . This book was released on 2015 with total page 107 pages. Available in PDF, EPUB and Kindle. Book excerpt: The American Cancer Society projects 221,200 new diagnoses and 158,040 deaths to occur in 2015 as a result of lung cancer. With a five-year relative survival rate that has only marginally improved from the 1970's (12%) to today (18%), new treatments are desperately needed for these large numbers of patients. Molecularly targeted therapies have begun to answer this call, with therapeutics against EGFR, ALK, and ROS1 now improving outcomes for patients with these specific genetic aberrations. However, the molecular events underlying lung cancer are complex, and many more therapeutic targets remain unidentified or untargeted. MERTK, a receptor tyrosine kinase of the TAM (TYRO3, AXL, and MERTK) family, is over-expressed or ectopically expressed in a wide variety of cancers, resulting in activation of several canonical oncogenic signaling pathways. Our laboratory has therefore begun developing novel therapeutics against MERTK. Described in Chapter III is Mer590, a monoclonal antibody that causes internalization and degradation of MERTK from the cell surface, resulting in decreased colony formation and increased apoptosis. The subject of Chapter IV, UNC2025, is an ATP-competitive small molecule inhibitor that blocks the kinase activity of MERTK, resulting in inhibition of downstream signaling, increased cell death, decreased colony formation, and decreased tumor formation in murine models. Although both of these agents show promising pre-clinical efficacy as single agents, they will not reach their full potential clinically unless given as part of a rational drug combination. Therefore, the identification of AXL as a target that has synergistic activity when inhibited in conjunction with MERTK is discussed in Chapter V. AXL and MERTK receptor levels are regulated in an inter-dependent manner, and a functional relationship is also present in which AXL inhibition allows for more potent inhibition by UNC2025 of MERTK kinase activity, downstream signaling pathways, and proliferative and colony forming phenotypes. Identifying rational combinations such as this will afford the novel MERTK compounds outlined in Chapters III and IV the greatest chance for success in clinical trials, and will help achieve the overarching goal of the laboratory - to add MERTK to the list of actionable oncogenic targets in clinical oncology.
Author : Anna V. Galkin
Publisher :
ISBN 13 :
Total Pages : 378 pages
Book Rating : 4.:/5 (763 download)
Download or read book Targeting Tyrosine Kinases in Solid Tumors and Hematopoietic Malignancies written by Anna V. Galkin and published by . This book was released on 2008 with total page 378 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tumorigenesis is commonly associated with the deregulation of Receptor Tyrosine Kinases (RTKs). Although not all mutated kinases provide a survival advantage, many have been shown to carry "driver" mutations and to be "causative" in tumor initiation and progression. The objective of this dissertation was to examine the potential contribution of two related orphan RTKs, anaplastic lymphoma kinase (ALK) and receptor tyrosine-kinase like orphan receptor-1 (Ror1) to tumorigenesis and examine their potential as therapeutic targets. ALK translocations are found in both solid and hematopoietic malignancies and are believed to be key components of these diseases. Approximately half of all anaplastic large-cell lymphoma (ALCL) cases are associated with the t(2;5;)(p23;q35) chromosomal translocation and its constitutively active fusion product, NPM-ALK. Chapter 2 introduces NVP-TAE684, a small molecule selective ALK inhibitor, and demonstrates its efficacy in targeting the NPM-ALK fusion kinase. Inhibition of NPM-ALK kinase activity in ALCL cells resulted in a significant reduction in cell survival both in vitro and in vivo . The biological role of Ror1 in cancer is less established, with some preliminary evidence suggesting a potential function of Ror1 as a "survival kinase". Chapters 3 and 4 identify the role of Ror1 as a mediator of canonical Wnt signaling and examine its expression in cancer cell lines and its contribution to non-small cell lung cancer (NSCLC) cell survival in vitro and in vivo. The development and validation of Ror1 targeting antibodies as therapeutic agents conclude Chapter 4. Understanding how newly identified RTKs contribute to the tumorigenic process and identifying patient populations dependent on these kinases will be invaluable in the design of novel therapeutic agents. While this dissertation focused on the investigation of two RTKs as potential targets, it also provides the framework for the methodology required to determine if other RTKs will prove to be valid therapeutic targets in cancer.
Author : Benjamin David Ferguson
Publisher :
ISBN 13 : 9781124867946
Total Pages : 169 pages
Book Rating : 4.8/5 (679 download)
Download or read book The Role of the EphB4 Receptor Tyrosine Kinase in Lung Cancer written by Benjamin David Ferguson and published by . This book was released on 2011 with total page 169 pages. Available in PDF, EPUB and Kindle. Book excerpt: Lung cancer is the most common cause of cancer death in the United States. Importantly, little progress has been made over the past three decades in its treatment success, highlighting the need for additional therapeutic targets. Receptor tyrosine kinases are frequently implicated in the progression of lung cancer, and some tyrosine kinase inhibitors are effective clinically. However, these inhibitors are frequently met with drug resistance and subsequent relapse, suggesting the importance of investigations into these mechanisms and alternative targets. The Eph RTK family, especially EphB4, has recently emerged as important players in cancer biology. Here, EphB4 is demonstrated to be overexpressed and mutated in lung cancer and to undergo copy number gains. Furthermore, inhibition of EphB4 reduces growth of lung cancer in vitro and in vivo, while expression of wild-type and mutant EphB4 promotes cell growth. Finally, investigation into EphB4 signaling reveals broad involvement in tyrosine kinase activity. Overall, this work represents the first systematic investigation of the role of EphB4 in lung cancer and identifies it as a novel therapeutic target.
Author : Richard A. Ward
Publisher : Royal Society of Chemistry
ISBN 13 : 1849731748
Total Pages : 333 pages
Book Rating : 4.8/5 (497 download)
Download or read book Kinase Drug Discovery written by Richard A. Ward and published by Royal Society of Chemistry. This book was released on 2012 with total page 333 pages. Available in PDF, EPUB and Kindle. Book excerpt: Kinase drug discovery remains an area of significant interest across academia and in the pharmaceutical industry. There are now around 13 FDA approved small molecule drugs which target kinases and many more compounds in various stages of clinical development. Although there have been a number of reviews/publications on kinase research, this book fills a gap in the literature by considering the current and future opportunities and challenges in targeting this important family of enzymes. The book is forward-looking and identifies a number of hot topics and key areas for kinase drug discovery over the coming years. It includes contributions from highly respected authors with a combined experience in the industry of well over 200 years, which has resulted in a book of great interest to the kinase field and across drug discovery more generally. Readers will gain a real insight into the huge challenges and opportunities which this target class has presented drug discovery scientists. The many chapters cover a wide breadth of topics, are well written and include high quality colour and black and white images. Topics covered include an outline of how medicinal chemistry has been able to specifically exploit this unique target class, along with reflections on the mechanisms of kinases inhibitors. Also covered is resistance to kinase inhibitors caused by amino acid mutations, case studies of kinase programs and reviews areas beyond protein kinases and beyond the human kinome. Also described are modern approaches to finding kinase leads and the book finishes with a reflection of how kinase drug discovery may progress over the coming years.
Author : Joseph Schlessinger
Publisher :
ISBN 13 : 9781936113330
Total Pages : 0 pages
Book Rating : 4.1/5 (133 download)
Download or read book Signaling by Receptor Tyrosine Kinases written by Joseph Schlessinger and published by . This book was released on 2014 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Receptor tyrosine kinases are cell-surface receptors that respond to numerous hormones and growth factors, including insulin, insulin-like growth factors, epidermal growth factor, and nerve growth factor. They activate highly conserved intracellular signaling pathways that regulate cell proliferation, differentiation, and metabolism, playing essential roles in developing and adult animals. This book examines the nature of these receptors and their ligands, the molecular mechanisms that they regulate within cells, and the roles of the receptors in normal physiology and control of embryogenesis. It also discusses how dysfunction of these mechanisms can contribute to cancer and other diseases.
