Egfr Signaling Networks In Cancer Therapy 2008

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EGFR Signaling Networks in Cancer Therapy

Author : John D. Haley
Publisher : Springer Science & Business Media
ISBN 13 : 1597453560
Total Pages : 393 pages
Book Rating : 4.5/5 (974 download)

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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.

EGFR Signaling Networks in Cancer Therapy (2008).

Author :
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (785 download)

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Book Synopsis EGFR Signaling Networks in Cancer Therapy (2008). by :

Download or read book EGFR Signaling Networks in Cancer Therapy (2008). written by and published by . This book was released on with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

The Application of Signaling Networks to Cancer Metastasis and Cellular Motility Through the EGFR Pathway

Author : Ranjeetha Bharath
Publisher :
ISBN 13 :
Total Pages : 86 pages
Book Rating : 4.:/5 (93 download)

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Book Synopsis The Application of Signaling Networks to Cancer Metastasis and Cellular Motility Through the EGFR Pathway by : Ranjeetha Bharath

Download or read book The Application of Signaling Networks to Cancer Metastasis and Cellular Motility Through the EGFR Pathway written by Ranjeetha Bharath and published by . This book was released on 2015 with total page 86 pages. Available in PDF, EPUB and Kindle. Book excerpt: This thesis explores the problem of cancer metastasis by analyzing the various downstream components of the epidermal growth factor receptor (EGFR) pathway. This work develops a mathematical model that consists of partial differential equations and signaling networks. Analysis techniques for these nonlinear reaction-diffusion equations included a study of the biological background and motivation, along with computational simulation of the various sets of models developed. The modeling effort combined biochemical reaction-diffusion equations for various species with mathematical descriptions of the mechanical machinery of the cell to characterize the foundations of cell movement in response to stimuli. By quantifying and qualifying the signaling networks and molecular pathways involved in cellular signaling and linking intracellular signaling to the mechanical machinery of the cell, it is possible to quickly check in silico the effects of changing various feedback parameters and signaling molecule concentrations. By creating a model of this process, it is possible to perform rapid tests of different pharmaceuticals on the biochemical and biomechanical pathways, in order to assess how they would affect cell motility and cancer metastasis on a large scale.

Functional Proteomic Analysis of Signaling Networks and Response to Targeted Therapy

Author :
Publisher :
ISBN 13 :
Total Pages : 20 pages
Book Rating : 4.:/5 (227 download)

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Book Synopsis Functional Proteomic Analysis of Signaling Networks and Response to Targeted Therapy by :

Download or read book Functional Proteomic Analysis of Signaling Networks and Response to Targeted Therapy written by and published by . This book was released on 2007 with total page 20 pages. Available in PDF, EPUB and Kindle. Book excerpt: The purpose of the research done has been to determine the regulation of the EGFR network and identify how manipulations of the network alter signal flow to bypass targeted inhibitions. The scope of the project is to understand the network and determine which molecules have to be targeted to inhibit tumor cell proliferation. The major finding thus far are 1) We have performed the proteomic analysis of the signaling network in a panel of 4 breast cancer cell lines and determined the network response to EGF and targeted inhibitors. 2) We have determined how information flows within the network and feedback regulation. 3) Using these biological data we have developed a computational model and have made predictions to identify combinations of targets. We have completed the tasks listed for this time period and are on track as indicated in the original grant.

Molecular Tools for Probing Signaling Networks of the EGFR Protein Kinase

Author : Ivan de Jesus Salazar Estrada
Publisher :
ISBN 13 :
Total Pages : 50 pages
Book Rating : 4.:/5 (951 download)

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Book Synopsis Molecular Tools for Probing Signaling Networks of the EGFR Protein Kinase by : Ivan de Jesus Salazar Estrada

Download or read book Molecular Tools for Probing Signaling Networks of the EGFR Protein Kinase written by Ivan de Jesus Salazar Estrada and published by . This book was released on 2015 with total page 50 pages. Available in PDF, EPUB and Kindle. Book excerpt: The epidermal growth factor receptor (EGFR) is one of the first and most extensively studied receptor tyrosine protein kinases and a validated drug target. Through protein phosphorylation EGFR orchestrates several signaling pathways that regulate cell growth and proliferation, and aberrant EGFR signaling has been reported in numerous cancer types. Several FDA-approved drugs target the ATP site of EGFR, and new therapeutics are in development that target the signaling partners of oncogenic EGFR. However, resistance is a challenge to overcome, and other EGFR-associated signaling proteins have been shown to confer resistance. Chemical probes may aid the elucidation of EGFR signaling networks for finding improved combination therapies. Here we report the sunthesis of first-generation biotinylated chemical probes 1a-1c targeting EGFR. These probes are based on the 4-aniloquinazoline core structure of gefitinib and erlotinib, two FDA-approved EGFR-targeting drugs. The probes 1a-1c exhibit excellent binding affinities for EGFR (Kd=23-41 nM). These probes are expected to serve as the basis for future development of next-generation multifunctional probes for understanding exogenous EGFR signaling networks.

Dissecting the Molecular Mechanisms of Therapeutic Resistance in Cancer

Author : Vibhuti Agrawal
Publisher :
ISBN 13 :
Total Pages : 181 pages
Book Rating : 4.:/5 (11 download)

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Book Synopsis Dissecting the Molecular Mechanisms of Therapeutic Resistance in Cancer by : Vibhuti Agrawal

Download or read book Dissecting the Molecular Mechanisms of Therapeutic Resistance in Cancer written by Vibhuti Agrawal and published by . This book was released on 2017 with total page 181 pages. Available in PDF, EPUB and Kindle. Book excerpt: Therapeutic resistance continues to be a persistent challenge in medical oncology. In clinical settings, resistance can occur at the beginning of treatment, or may be acquired after an initial clinical response to the therapy. Several mechanisms of drug resistance have been described in cancer, including alterations in the drug transport and metabolism process, mutations in drug-target, activation of bypass signaling pathways, inhibition of cell-death pathways, and induction of an epithelial to mesenchymal transition (EMT) in response to cytotoxic or targeted therapies. In this study, I have investigated the molecular mechanisms underlying ZEB 1-induced EMT and established a new computational framework that uses inter-animal heterogeneity to identify drivers responsible for variable phenotypic responses across different animals. EMT describes a cell-state switching process wherein epithelial cells lose their tight cell-cell junction contacts, and acquire the ability to migrate and invade the surrounding stroma to enter into blood circulation. Given the widespread role of EMT in drug resistance, it is imperative to identify therapeutic strategies to inhibit this transition. To identify druggable targets to block EMT progression, and therefore overcome EMT-mediated therapeutic resistance, I studied the effects of ZEB 1 expression on cellular signaling networks. By quantifying changes in tyrosine phosphorylation at different time points during ZEB 1-induced EMT, I found that Src family kinases (SFKs) were activated within 24 hours of ZEB 1 expression. Inhibition of SFKs blocked not only ZEB 1-induced EMT, but also EMT initiated by TGFp- and EGF signaling pathways in both breast and NSCLC cell-lines. SFK inhibition also prevented EGFR inhibitor-induced EMT and drug resistance in NSCLC cells both in vitro and in vivo. Mechanistically, SFK activation stabilized ZEBI by promoting ERK1/2-mediated phosphorylation on three serine residues, S583, S646, and S679. Consequently, MEK inhibition phenocopied the effects of blocking SFK activity with regards to decreasing stability of ZEB 1 and inhibiting ZEB 1-induced EMT. These results provide a new therapeutic application of SFK inhibitors as a potential anti-EMT therapy, to enhance the susceptibility of cancer cells to chemo- or targeted therapies. In the second part of this thesis, I have described a computational framework that leverages inter-animal heterogeneity to identify molecular mechanisms underlying variable phenotypic responses across different animals. Substantial inter-animal variability in phenotypes within the same treatment group, limits our ability to draw conclusions or gain meaningful insights about a biological process by simply averaging the data. To identify molecular drivers for heterogeneous phenotypic responses, I have established a method where each animal is considered as an individual entity whose phenotypic response is dependent on the state of its underlying signaling networks. As a proof of concept, I have used this method to successfully predict the resistance mechanisms of CDK4/6 inhibitor, palbocilib in two GBM PDX and one MPNST PDX models. The GBM6 model activated EGFR signaling upon treatment with palbociclib whereas the GBM22 and MPNST3 models activated SFKs and PDGFRa signaling in resistant tumors. Across all three PDX tumor models, treatment with combination therapies, consisting of palbociclib and an inhibitor targeting the activated bypass signaling pathway, substantially prolonged survival of mice. Thus, these results suggest that inter-animal variability can be used as a tool to predict drivers for a specific phenotypic response across different treatment conditions.

Cancer Signaling

Author : Christoph Wagener
Publisher : John Wiley & Sons
ISBN 13 : 352780045X
Total Pages : 357 pages
Book Rating : 4.5/5 (278 download)

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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.

Pancreatic Cancer

Author : Douglas B. Evans
Publisher : Springer Science & Business Media
ISBN 13 : 0387216006
Total Pages : 413 pages
Book Rating : 4.3/5 (872 download)

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Book Synopsis Pancreatic Cancer by : Douglas B. Evans

Download or read book Pancreatic Cancer written by Douglas B. Evans and published by Springer Science & Business Media. This book was released on 2006-04-18 with total page 413 pages. Available in PDF, EPUB and Kindle. Book excerpt: The MD Anderson Solid Tumor Oncology series presents cutting-edge surgical treatment and medical therapy for specific sites. This volume, Pancreatic Cancer, addresses epidemiology and molecular biology, inherited syndromes, staging, surgical techniques, multimodality therapy, and emerging therapies. The individual chapters focus on narrow, specific topics to produce a reference work of value to those interested in pancreatic cancer from a clinical and translational research perspective. A must-have for surgical oncologists and general surgeons.

Encyclopedia of Signaling Molecules

Author : Sangdun Choi
Publisher : Springer
ISBN 13 : 9781493968008
Total Pages : 6330 pages
Book Rating : 4.9/5 (68 download)

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Book Synopsis Encyclopedia of Signaling Molecules by : Sangdun Choi

Download or read book Encyclopedia of Signaling Molecules written by Sangdun Choi and published by Springer. This book was released on 2017-12-15 with total page 6330 pages. Available in PDF, EPUB and Kindle. Book excerpt: The second edition of this encyclopedia presents over 400 biologically important signaling molecules and the content is built on the core concepts of their functions along with early findings written by some of the world’s foremost experts. The molecules are described by recognized leaders in each molecule. The interactions of these single molecules in signal transduction networks will also be explored. This encyclopedia marks a new era in overview of current cellular signaling molecules for the specialist and the interested non-specialist alike. Currently, there are more than 30,000 genes in human genome. However, not all the proteins encoded by these genes work equally in order to maintain homeostasis. Understanding the important signaling molecules as completely as possible will significantly improve our research-based teaching and scientific capabilities.

Signal Transduction in Cancer

Author : David A. Frank
Publisher : Springer Science & Business Media
ISBN 13 : 1402073402
Total Pages : 358 pages
Book Rating : 4.4/5 (2 download)

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Book Synopsis Signal Transduction in Cancer by : David A. Frank

Download or read book Signal Transduction in Cancer written by David A. Frank and published by Springer Science & Business Media. This book was released on 2002-12-31 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: One of the most exciting areas of cancer research now is the development of agents which can target signal transduction pathways that are activated inappropriately in malignant cells. The understanding of the molecular abnormalities which distinguish malignant cells from their normal counterparts has grown tremendously. This volume summarizes the current research on the role that signal transduction pathways play in the pathogenesis of cancer and how this knowledge may be used to develop the next generation of more effective and less toxic anticancer agents. Series Editor comments: "The biologic behavior of both normal and cancer cells is determined by critical signal transduction pathways. This text provides a comprehensive review of the field. Leading investigators discuss key molecules that may prove to be important diagnostic and/or therapeutic targets."

Signaling by Receptor Tyrosine Kinases

Author : Joseph Schlessinger
Publisher :
ISBN 13 : 9781936113330
Total Pages : 0 pages
Book Rating : 4.1/5 (133 download)

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Book Synopsis Signaling by Receptor Tyrosine Kinases by : Joseph Schlessinger

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.

Successes and Limitations of Targeted Cancer Therapy

Author : S. Peters
Publisher : Karger Medical and Scientific Publishers
ISBN 13 : 3318025429
Total Pages : 126 pages
Book Rating : 4.3/5 (18 download)

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Book Synopsis Successes and Limitations of Targeted Cancer Therapy by : S. Peters

Download or read book Successes and Limitations of Targeted Cancer Therapy written by S. Peters and published by Karger Medical and Scientific Publishers. This book was released on 2014-02-19 with total page 126 pages. Available in PDF, EPUB and Kindle. Book excerpt: The treatment of patients with advanced malignancies has undergone remarkable change in the last few years. While in the past decisions about systemic therapy were largely based on the performance status of a patient, oncologists today also take into account the pathological and molecular characteristics of the patient’s tumor. Targeting specific molecular pathways important for tumorigenesis has become the preferred way of treatment for many types of malignancies. With these advances come new challenges including the optimization of therapy, recognizing and dealing with side effects and, importantly, the development of resistance. This book provides an up-to-date overview of the advances and limitations of targeted therapy for several tumor entities including breast cancer, colon cancer, gastrointestinal stromal tumors, lung cancer, melanoma, ovarian cancer and renal cell carcinoma. Written by over a dozen internationally renowned scientists, the book is suitable for advanced students, postdoctoral researchers, scientists and clinicians who wish to update their knowledge of the latest approaches to targeted cancer therapies.

Extracellular Matrix: Pathobiology and Signaling

Author : Nikos Karamanos
Publisher : Walter de Gruyter
ISBN 13 : 3110258773
Total Pages : 940 pages
Book Rating : 4.1/5 (12 download)

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Book Synopsis Extracellular Matrix: Pathobiology and Signaling by : Nikos Karamanos

Download or read book Extracellular Matrix: Pathobiology and Signaling written by Nikos Karamanos and published by Walter de Gruyter. This book was released on 2012-08-31 with total page 940 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the last decades cell biology and biological chemistry have increasingly turned their attention to the space between cells and revealed an elaborate network of macromolecules essential for structural support, cell adhesion and signaling. This comprehensive handbook of the extracellular matrix will give an overview of the current state of knowledge of matrix components (structure and function), their role in heath and disease (matrix pathobiology) and new aspects related to pharmacological targeting. It will provide an introduction to the extracellular matrix and detailed sections and chapters on: Importance of extracellular matrix in health and disease Matrix proteoglycans (aggrecan, versican, perlecan, SLRPs, syndecans, glypicans, serglycin) Matrix proteinases (remodeling, would healing, regulatory roles in health and disease, metalloproteinases, cystein proteases, plasmin and plasminogen activator system) Glycobiology (hyaluronan and sulfated glycosaminoglycans in cancer, inflammation and metabolic control) Collagens (supramolecular assembly, proteins binding collagen, scaffolds, bacterial and mutated collagens, procollagen proteinases) Cell surface receptors (integrins, syndecans, mechanical strain and TGFb, CD44 and DDR). Biotechnological and pharmacological outlook (matrix regulation by growth factors, hyaluronidases, pathobiology, disease targeting, delivery systems, EMT and proteomics). "The book Extracellular Matrix: Pathobiology and Signaling provides a comprehensive and up to date collection of very relevant topics for understanding the various facets of extracellular matrix and its interactions with cells in normal tissue as well as in disease. It represents the current front-line and will serve as a reference for extracellular matrix and posttranslational modifications." Dick Heinegård, Department of Clinical Sciences Lund, Section Rheumatology, Lund University, Sweden

Webster's New World Medical Dictionary

Author :
Publisher :
ISBN 13 : 9781784027834
Total Pages : pages
Book Rating : 4.0/5 (278 download)

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Book Synopsis Webster's New World Medical Dictionary by :

Download or read book Webster's New World Medical Dictionary written by and published by . This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Webster's New World Medical Dictionary, Third Edition will help you understand and communicate your medical needs when it matters the most. Written by doctors and the experts at WebMD, this edition includes 8500 entries, including 500 new terms, a vitamin appendix, and a companion website to give you access to medical language.

Rise and Fall of Epithelial Phenotype

Author : Pierre Savagner
Publisher : Springer Science & Business Media
ISBN 13 : 0387286713
Total Pages : 341 pages
Book Rating : 4.3/5 (872 download)

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Book Synopsis Rise and Fall of Epithelial Phenotype by : Pierre Savagner

Download or read book Rise and Fall of Epithelial Phenotype written by Pierre Savagner and published by Springer Science & Business Media. This book was released on 2007-07-05 with total page 341 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epithelial phenotype is a dynamic stage of differentiation that can be modulated during several physiological or pathological events. The rapid conversion to a mesenchymal-like phenotype is called an epithelial-mesenchymal transition (EMT). The Rise and Fall of Epithelial Phenotype is the first book to comprehensively introduce the concept of EMT. The first part of this volume describes main examples and models and explains their physiological relevance. These examples include hydra morphogenesis, gastrulation in mouse, drosophila and sea urchin, as well as neural crest cell migration and heart morphogenesis in vertebrates. Part two reviews in detail, specific EMT molecular pathways covering extracellular induction, transduction and transcription response and modulation of cell-cell adhesion structures. It emphasizes new specific pathways with potential medical applications. EMTs can also be linked to pathological events such as wound healing and cancer progression, as detailed in this section of the book.

HER2-Positive Breast Cancer

Author : Sara Hurvitz
Publisher : Elsevier Health Sciences
ISBN 13 : 0323581234
Total Pages : 264 pages
Book Rating : 4.3/5 (235 download)

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Book Synopsis HER2-Positive Breast Cancer by : Sara Hurvitz

Download or read book HER2-Positive Breast Cancer written by Sara Hurvitz and published by Elsevier Health Sciences. This book was released on 2018-07-26 with total page 264 pages. Available in PDF, EPUB and Kindle. Book excerpt: Get a quick, expert overview of clinically-focused topics and guidelines that are relevant to testing for HER2, which contributes to approximately 25% of breast cancers today. This concise resource by Drs. Sara Hurvitz, and Kelly McCann consolidates today’s available information on this growing topic into one convenient resource, making it an ideal, easy-to-digest reference for practicing and trainee oncologists.

Molecular Pathology of Lung Cancer

Author : Philip T. Cagle
Publisher : Springer Science & Business Media
ISBN 13 : 1461431972
Total Pages : 217 pages
Book Rating : 4.4/5 (614 download)

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Book Synopsis Molecular Pathology of Lung Cancer by : Philip T. Cagle

Download or read book Molecular Pathology of Lung Cancer written by Philip T. Cagle and published by Springer Science & Business Media. This book was released on 2012-06-14 with total page 217 pages. Available in PDF, EPUB and Kindle. Book excerpt: As with other books in the Molecular Pathology Library Series, Molecular Pathology of Lung Cancer bridges the gap between the molecular specialist and the clinical practitioner, including the surgical pathologist who now has a key role in decisions regarding molecular targeted therapy for lung cancer. Molecular Pathology of Lung Cancer provides the latest information and current insights into the molecular basis for lung cancer, including precursor and preinvasive lesions, molecular diagnosis, molecular targeted therapy, molecular prognosis, molecular radiology and related fields for lung cancer generally and for the specific cell types. As many fundamental concepts about lung cancer have undergone revision in only the past few years, this book will likely be the first to comprehensively cover the new molecular pathology of lung cancer. It provides a foundation in this field for pathologists, medical oncologists, radiation oncologists, thoracic surgeons, thoracic radiologists and their trainees, physician assistants, and nursing staff.