BRAF Targets in Melanoma: Biological Mechanisms, Resistance, and Drug Discovery PDF
Preview BRAF Targets in Melanoma: Biological Mechanisms, Resistance, and Drug Discovery
Cancer Drug Discovery and Development Volume 82 Series Editor Beverly A. Teicher Bethesda, Maryland, USA Cancer Drug Discovery and Development, the Springer series headed by Beverly A. Teicher, is the definitive book series in cancer research and oncology. Volumes cover the process of drug discovery, preclinical models in cancer research, specific drug target groups, and experimental and approved therapeutic agents. The volumes are current and timely, anticipating areas where experimental agents are reaching FDA approval. Each volume is edited by an expert in the field covered, and chapters are authored by renowned scientists and physicians in their fields of interest. For more information about this series, go to http://www.springer.com/series/7625 Ryan J. Sullivan Editor BRAF Targets in Melanoma Biological Mechanisms, Resistance, and Drug Discovery Editor Ryan J. Sullivan Center for Melanoma Massachusetts General Hospital Cancer Center Boston Massachusetts USA ISSN 2196-9906 ISSN 2196-9914 (electronic) ISBN 978-1-4939-2142-3 ISBN 978-1-4939-2143-0 (eBook) DOI 10.1007/978-1-4939-2143-0 Springer New York Heidelberg Dordrecht London Library of Congress Control Number: 2014955080 © Springer Science+Business Media New York 2015 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Contents 1 Melanoma: Historical Context ................................................................ 1 Suraj Venna, Sekwon Jang and Michael Atkins 2 Melanoma Pathogenesis .......................................................................... 25 Jennifer A. Lo and David E. Fisher 3 Molecular Diagnostics and Tumor Mutational Analysis ...................... 47 Melissa A. Wilson and Katherine L. Nathanson 4 Clinical Utility of BRAF-Targeted Therapy in Melanoma .................. 67 Jeffrey A. Sosman and Douglas B. Johnson 5 T he Ethics of Randomized Trials in Oncology ...................................... 85 Pallavi Kumar and Ryan J. Sullivan 6 Parallel and Serial Blockade Strategies in BRAF-Mutant Melanoma ....................................................................... 105 Michael A. Davies 7 T argeting the Cell Cycle and p53 in Combination with BRAF-Directed Therapy ......................................................................... 137 Dale Han and Keiran SM Smalley 8 Combination BRAF-Directed Therapy and Immunotherapy ............. 163 Zachary A. Cooper, Zain Ahmed and Jennifer A. Wargo 9 M oving Forward: Making BRAF-Targeted Therapy Better ............... 183 Keith T. Flaherty Index ................................................................................................................ 203 v Contributors Zain Ahmed Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA Michael B. Atkins Medstar Washington Cancer Institute, Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington DC, USA Zachary A. Cooper Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA Michael A. Davies Departments of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA Departments of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA David E. Fisher Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA, USA Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA Keith T. Flaherty Massachusetts General Hospital Cancer Center, Boston, MA, USA Dale Han Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA Sekwon Jang Medstar Washington Cancer Institute, Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington DC, USA vii viii Contributors Douglas B. Johnson Vanderbilt University School of Medicine, Vanderbilt- Ingram Cancer Center, Nashville, TN, USA Pallavi Kumar Center for Melanoma, Massachusetts General Hospital Cancer Center, Boston, MA, USA Jennifer A. Lo Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA, USA Katherine L. Nathanson Division of Translational Medicine and Human Genetics, Department of Medicine Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA Keiran SM Smalley Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA Department of Molecular Oncology, Moffitt Cancer Center, Tampa, FL, USA Jeffrey A. Sosman Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA Ryan J. Sullivan Center for Melanoma, Massachusetts General Hospital Cancer Center, Boston, MA, USA Suraj Venna Medstar Washington Cancer Institute, Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington DC, USA Jennifer A. Wargo Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA Melissa A. Wilson Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA Chapter 1 Melanoma: Historical Context Suraj Venna, Sekwon Jang and Michael Atkins Abstract We are in the midst of a therapeutic revolution for patients with mela- noma. This chapter reviews several topics on melanoma from epidemiologic trends, to the evolution of the surgical approach, to adjuvant treatment of melanoma, and also reviews various systemic therapies for metastatic melanoma. Each component of this chapter describes advances from a historical perspective, beginning with the first descriptions of melanoma in the literature, to the discovery of activating B-raf mutations in melanoma, and concluding with the current immune and targeted based therapies for advanced melanoma. It serves as a segue to the more detailed therapies and advances in the ensuing chapters. Keywords B-raf · Checkpoint inhibition · Adjuvant therapy · Chemotherapy · Biochemotherapy · Immunotherapy · MC1R · Risk factors · Sentinel lymph node biopsy · Vaccines 1.1 Introduction John Hunter in 1787 excised a tumor from the jaw of a young man and aptly described it as a “cancerous fungous excrescence.” Hunter detailed that the tumor recurred on the patients chin several years later, thought to perhaps have been in- cited by trauma as this young gentleman had partaken in a bar room brawl at that time. This specimen was preserved for nearly 200 years in the Hunterian Museum of the Royal College of Surgeons in London and is now specimen number 219 [1]. In 1968 the specimen was examined and verified to be melanoma. Rene Laennec in 1806 is credited as the first physician in modern times to describe melanoma as a disease and published this while still a medical student [2]. William Norris in 1820 M. B. Atkins () New Research Building, Rm E501, 3970 Reservoir Rd, NW, Washington DC 20056, USA e-mail: [email protected] S. Venna · S. Jang · M. B. Atkins Medstar Washington Cancer Institute, Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington DC, USA © Springer Science+Business Media New York 2015 1 R. J. Sullivan (ed.), BRAF Targets in Melanoma, Cancer Drug Discovery and Development 82, DOI 10.1007/978-1-4939-2143-0_1 2 S. Venna et al. published his post-mortem description of a patient with atypical nevi who devel- oped and died of metastatic melanoma: “On making an incision through the origi- nal tumour, I found the texture to be heterogeneous; it was of a reddish and whitish brown tint throughout, not very unlike the internal structure of a nutmeg. The newly formed tumour, and the tubera around, though during life they wore a very dif- ferent aspect, after death both exhibited the same dark-coloured appearance. On puncturing a considerable number of the different tubercles, a thick dark fluid was discharged from them [3].” The first formal acknowledgement that melanoma, in advanced stages, is untreatable and a death sentence, was documented in 1844 by Samuel Cooper in his textbook First lines of theory and practice of surgery [4]. He published that the only chance for survival was early removal of the disease, stating that “No remedy is known of, for melanosis….the only chance of benefit depends upon the early removal of the disease by operation….” However, the earliest ex- ample of melanoma has been suggested to come from Mummified skeletal remains of Peruvian Incas dating to 2400 BC [5]. Over time, we have moved from simple descriptive terms such as cancerous fungous excrescence, to defining the molecular pathways responsible for the development of melanoma. This has elegantly been now translated into targeted therapies for melanoma that provide the expectation of controlling this often devastating disease in significant subsets of patients for increasingly extended periods of time. After a nearly 15 year stand-still for the treatment of metastatic melanoma, we are in the midst of a virtual revolution in systemic treatment of patients with mela- noma. The targeted therapy era for melanoma was initiated by the finding that a significant proportion of melanomas carry activating mutations in a component of the mitogen activated protein kinase (MAPK) signaling pathway. Activating muta- tions in B-raf were identified in 2002 and also found to occur in the vast majority of benign nevi (80 %) [6, 7]. These findings led to a resurgence of interest in melanoma but also led to continued interrogation of the MAPK pathway and other pathways. The discovery of B-raf mutations in benign nevi made it clear that this may be a necessary but early step in melanoma progression and other critical targets must also be involved. 1.2 Epidemiologic Trends Melanoma accounts for 5 % of all skin cancers but is the major cause of death from skin cancer. In the year 2013, there were an estimated 76,690 new cases of invasive melanoma in the United States and over 9480 deaths attributable to melanoma [8]. This equates to one melanoma-specific death every hour. The number of annual new cases is likely underestimated given that in-situ lesions and thin invasive mela- nomas (Stage 1a) are not consistently reported to tumor registries, being excised in the outpatient and private practice settings [9]. The lifetime incidence of develop- ing melanoma in the United States was 1/1500 for individuals born in the early 1900’s [10]. Between 1950 and 2000, there was an explosive increase in melanoma
The list of books you might like
