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Advances in Experimental Medicine and Biology 893 Aamir Ahmad Shirish Gadgeel Editors Lung Cancer and Personalized Medicine Current Knowledge and Therapies A dvances in Experimental Medicine and Biology More information about this series at h ttp://www.springer.com/series/5584 A amir A hmad • S hirish G adgeel E ditors L ung Cancer and Personalized Medicine C urrent Knowledge and Therapies E ditors A amir A hmad S hirish G adgeel K armanos Cancer Institute K armanos Cancer Institute W ayne State University Wayne State University D etroit, M I, U SA Detroit, M I, U SA I SSN 0065-2598 ISSN 2214-8019 (electronic) Advances in Experimental Medicine and Biology ISBN 978-3-319-24221-7 ISBN 978-3-319-24223-1 (eBook) D OI 10.1007/978-3-319-24223-1 L ibrary of Congress Control Number: 2015959573 S pringer Cham Heidelberg New York Dordrecht London © Springer International Publishing Switzerland 2 016 T his work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms 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. T he use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. T he publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. P rinted on acid-free paper S pringer International Publishing AG Switzerland is part of Springer Science+Business Media (www.springer.com) P refa ce L ung cancer is one of the most common causes of cancer-related deaths in the world, affecting millions of individuals. This volume, L ung Cancer and Personalized Medicine: Current Updates and Therapies, comprehensively reviews lung cancer as a disease, details the current state of our knowledge, and showcases the promising novel strategies being pursued. With a greater understanding of lung cancer, we can better appreciate the heterogeneity among lung cancer patients. It is now more evi- dent than ever before that a “one-size-fi ts-all” approach is not an effective means of clinical management of patients. It is critical to understand every lung cancer patient as an individual, the unique genomic make up an individual patient possesses, and the unique opportunities that such understandings present in developing a treatment plan to which an individual is most likely to respond—that is, “personalized management,” the focus of this volume. Chapter 1 provides a commentary on lung cancer statistics. It is important that we remind ourselves of the threats posed by lung cancer. It is the leading cause of cancer-related mortality in men in the USA and throughout the world. In women, it is the leading cause of cancer-related deaths in the USA, but ranks second worldwide. This chapter provides a detailed overview of variations in lung cancer rates and trends in the USA as well as globally. Chapter 2 , which addresses the epidemiology of lung cancer, touches upon the various risk factors that may predispose an individual to the disease. Availability of putative risk prediction models will, undoubtedly, change the personalized care of lung cancer patients. Cigarette smoking has always been considered a major factor contributing to lung cancer. However, a substantial number of lung cancer patients never smoked. As a separate entity, lung cancer among nonsmokers will rank as the seventh leading cause of cancer-related deaths, which is discussed in Chapter 3 . C hapter 4 , on immune therapy, addresses the recent advances in immune responses in lung cancer patients—previously believed to be irrelevant to lung cancer treatment. This chapter discusses the various immunotherapeutic approaches for treatment of lung cancer patients, including those in clinical trials. With the realiza- tion that angiogenesis is frequently upregulated in lung cancer patients, the focus on antiangiogenic agents is of relevance to personalized therapy of lung cancer patients—which is discussed in Chapter 5 , which outlines the progress as well as v vi Preface c hallenges associated with the antiangiogenic therapy in non-small cell vs. small cell lung cancers. Chapter 6 discusses the targets of personalized therapy in lung cancer, namely, the tyrosine kinases, with a focus on epidermal growth factor recep- tor (EGFR) mutational status. With such important role of tyrosine kinases in lung cancer progression, tyrosine kinase inhibitors have been studied in considerable detail, but acquired resistance to these inhibitors remains a major clinical challenge. These challenges and the mechanisms of resistance to EGFR-targeted therapies are discussed in Chapter 7 , which also touches upon the novel strategies to overcome the resistance. Chapter 8 focuses on KRAS-mutant lung cancers that make up approximately a quarter of all lung cancers. KRAS mutations have also been linked to EGFR-resistance, and their importance in lung cancer progression is increasingly being realized. Chapter 9 focuses on anaplastic lymphoma kinase (ALK), another tyrosine kinase whose chromosomal rearrangement results in aggressive lung cancers. The evolving knowledge on ALK-rearranged lung cancers is of relevance to the personalized management of patients. Rounding up our knowledge on the resistance to current therapies, Chapter 1 0 summarizes the various chemotherapy options available for lung cancer patients and the associated resistance pathways. Finally, Chapter 1 1 summarizes the chemistry of metal-based drugs, particularly those based on platinum, ruthenium, gadolinium, and iron compounds. A better understanding of metal-based compounds promises to deliver novel targeted drugs that can potentially be personalized for individual patients. P art II of this volume, available as a separate volume, addresses the many novel and emerging therapies that can potentially change the way individual lung cancer patients are treated in clinics. Combined, the two volumes provide a detailed overview of topics that are critical to the personalized management of lung cancer. D etroit, M I, U SA A amir A hmad S hirish G adgeel A cknowledgments We, the editors, thank all the authors who worked hard and contributed their knowledge to this volume. Our special thanks to Springer for entrusting us with this exciting project. Our contacts at Springer Publishers—Fiona Sarne at the start of project and Joy Bramble at the end of the project—made sure that we stayed on course; their enormous help is highly appreciated. vii C ontents L ung Cancer Statistics .................................................................................... 1 L indsey A. T orre, R ebecca L. S iegel, and A hmedin J emal E pidemiology of Lung Cancer ....................................................................... 2 1 A nn G . S chwartz and M ichele L . C ote L ung Cancer in Never Smokers ..................................................................... 4 3 G abriel A lberto R ivera and H eather W akelee I mmune Therapy ............................................................................................ 5 9 L ysanne L ievense, J oachim A erts, and J oost H egmans A nti-angiogenesis in Personalized Therapy of Lung Cancer ...................... 9 1 P eter M . E llis T arget Therapy in Lung Cancer .................................................................... 1 27 S tefano C afarotti, F ilippo L ococo, P atrizia F roesh, F rancesco Z appa, and D utly A ndrè M echanisms of Resistance to EGFR Tyrosine Kinase Inhibitors and Therapeutic Approaches: An Update .................................................... 1 37 A arif A hsan K RAS-Mutant Lung Cancers in the Era of Targeted Therapy ................... 1 55 J arushka N aidoo and A lexander D rilon A naplastic Lymphoma Kinase (ALK) Signaling in Lung Cancer .............. 1 79 S ai-Hong I gnatius O u and K eisuke S hirai C hemotherapy Resistance in Lung Cancer .................................................. 1 89 E ric S . K im ix