Table Of ContentAdvances in Experimental Medicine and Biology 890
Aamir Ahmad
Shirish M. Gadgeel Editors
Lung Cancer and
Personalized Medicine:
Novel Therapies and
Clinical Management
A dvances in Experimental Medicine and Biology
Volume 890
Editorial Board:
IRUN R. COHEN, The Weizmann Institute of Science, Rehovot, Israel
ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA
JOHN D. LAMBRIS, University of Pennsylvania, Philadelphia, PA, USA
RODOLFO PAOLETTI, University of Milan, Milan, Italy
M ore information about this series at h ttp://www.springer.com/series/5584
A amir A hmad • S hirish M . Gadgeel
E ditors
L ung Cancer and
Personalized Medicine:
Novel Therapies
and Clinical Management
E ditors
A amir A hmad S hirish M . Gadgeel
K armanos Cancer Institute K armanos Cancer Institute
W ayne State University W ayne State University
D etroit, M I, U SA D etroit, M I, U SA
I SSN 0065-2598 ISSN 2214-8019 (electronic)
Advances in Experimental Medicine and Biology
ISBN 978-3-319-24931-5 ISBN 978-3-319-24932-2 (eBook)
D OI 10.1007/978-3-319-24932-2
L ibrary of Congress Control Number: 2015960242
S pringer Cham Heidelberg New York Dordrecht London
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P refa ce
T his is the second part of volume L ung Cancer and Personalized Medicine. Part I of
this volume, available as a separate book, discussed lung cancer as a disease, the
available therapies and the associated challenges. In this edition, we focus on the
upcoming and novel strategies to better understand and target lung cancer. As dis-
cussed in the chapters presented here, our understanding of lung cancer and the vari-
ous factors associated with its onset and progression has vastly improved in last
several years. All this information is critical to developing personalized therapies
tailored for the benefi t of individual patients.
A major component of personalized therapy is the ability to profi le an individual
lung cancer patient. The molecular and genomic profi ling of lung cancers are steps
in this direction. C hapter 1 focuses on the advancements in these areas of lung can-
cer research. C hapter 2 summarizes all of the emerging biomarkers, relevant to
personalized care of lung cancer patients. This chapter discusses the many potential
biomarkers, such as ROS1, RET, MET, HER2 and BRAF that are under investiga-
tion. This is in addition to EGFR and ALK, the more established biomarkers cov-
ered in more detailed chapters in part I of this volume. For a successful personalized
profi ling of lung cancer patients, a comprehensive signature, with relative status of
multiple biomarkers, is very critical. C hapter 3 focuses on the process of epithelial
to mesenchymal transition (EMT), a phenomenon that is particularly relevant to
metastasis of lung cancers. The important role that EMT plays in acquisition of
stem cell-like properties and resistance to targeted therapies is now well accepted,
and all these topics are covered in this chapter.
C hapter 4 continues on the topic of cancer stem cells (CSCs) and provides a
more detailed overview of our knowledge on the topic. The existence of CSCs has
been a hotly debated topic for last several years. In addition to the various markers
and a role of CSCs in the recurrence and drug resistance mechanisms of lung can-
cers, this chapter also describes the emerging evidence of natural agents and their
synthetic derivatives as compounds that can effectively target CSCs. C hapter 5
details the current knowledge of lung cancer cells’ niche—the microenvironment—
which feeds and sustains lung cancer cells, providing them the perfect environment
to acquire an aggressive phenotype. A better understanding of tumor microenvironment
v
vi Preface
is critical to the development of future personalized therapies for lung cancer
patients. The next chapter, C hapter 6 , examines the epigenetic changes associated
with lung cancer progression and their possible validation as therapeutic targets.
This chapter discusses the epigenetic changes that are now known to infl uence the
expression of oncogenes as well as the tumor suppressors, and the various epigen-
etic events that can potentially be targeted as part of personalized management of
lung cancer patients.
C hapter 7 provides a detailed overview of next-generation sequencing and the
associated promise of early detection and molecular profi ling of lung cancers. The
importance of early detection and complete profi ling cannot be over-stated, and,
moving forward, such methodologies will be very handy at the time of making deci-
sions for personalized treatment plans. C hapter 8 discusses the promising fi eld of
‘cancer nanomedicine’. The nanoparticle-based systems, discussed in this chapter,
can be an invaluable tool in the delivery of novel therapeutic agents in an attempt to
enhance their effectiveness. According to the American Cancer Society, lung cancers
are three distinct types: non-small cell lung cancers; small cell lung cancers; and lung
carcinoid tumors. While non-small cell lung cancers represent a major subtype with
up to 85% of all lung cancers, small cell lung cancers are known to be particularly
aggressive. C hapter 9 describes the recent updates towards personalized therapy of
small cell lung cancers.
The foregoing chapters address the various characteristics of lung cancers and
the putative targets of therapy, knowledge of which is essential to the development
of personalized clinical management. The manner in which the personalized
approach is actually applied in clinical management of lung cancers is discussed in
the last two chapters of this section. Radiation therapy is a major treatment option
for lung cancers, and Chapter 1 0 discusses the concept of personalized radiation
therapy that promises to improve treatment outcomes with substantially reduced
toxicity. Finally, Chapter 1 1 details the approaches to making a decision for person-
alized treatment of lung cancer patients, based on the individual clinical character-
istics, biomarkers and other parameters that an individual lung cancer patient
presents.
B etween the two parts, this volume comprehensively covers many aspects of
modern day lung cancer research, with special focus on personalized therapy. We
are so excited to have a panel of experts and leading lung cancer scientists contrib-
ute to this volume, and it is our distinct pleasure to present this volume to the scien-
tifi c community.
D etroit, USA Aamir A hmad, P hD
Shirish M . Gadgeel, M D
C ontents
L ung Cancer Genomics in the Era of Accelerated Targeted
Drug Development .......................................................................................... 1
P riyanga W ijesinghe and A liccia B ollig-Fischer
E merging Biomarkers in Personalized Therapy of Lung Cancer .............. 2 5
P hilip T . C agle, K irtee R aparia, and B ryce P . P ortier
E pithelial Mesenchymal Transition in Aggressive Lung Cancers .............. 3 7
V ivek M ittal
T he Role of Cancer Stem Cells in Recurrent and Drug-Resistant
Lung Cancer .................................................................................................... 5 7
R aagini S uresh, S hadan A li, A amir A hmad, P hilip A . P hilip,
and F azlul H . S arkar
T he Microenvironment of Lung Cancer
and Therapeutic Implications ........................................................................ 7 5
V ivek M ittal, T ina El R ayes, N avneet N arula, T imothy E . M cGraw,
N asser K. A ltorki, and M ary H elen Barcellos-Hoff
E pigenetics in Personalized Management of Lung Cancer ......................... 1 11
A amir A hmad
N ext-Generation Sequencing and Applications to the Diagnosis
and Treatment of Lung Cancer ..................................................................... 1 23
K ristina M . K ruglyak, E rick L in, and F rank S . O ng
N anomedicine for Treatment of Lung Cancer ............................................. 1 37
S ajid H ussain
P ersonalized Therapy of Small Cell Lung Cancer ....................................... 1 49
B ryan J . S chneider and G regory P . K alemkerian
vii
viii Contents
P ersonalized Radiation Therapy (PRT) for Lung Cancer .......................... 1 75
J ian-Yue J in and F eng-Ming (Spring) K ong
P ersonalized Therapy of Non-Small Cell Lung Cancer (NSCLC) ............. 2 03
S hirish M . Gadgeel
I ndex ................................................................................................................. 2 23
C ontributors
A amir A hmad K armanos Cancer Institute, Wayne State University, Detroit,
MI, USA
S hadan A li D epartment of Oncology, Karmanos Cancer Institute, Wayne State
University School of Medicine, Detroit, MI, USA
N asser K. A ltorki D epartment of Cardiothoracic Surgery, Weill Medical College
of Cornell University, New York, NY, USA
Neuberger Berman Lung Cancer Research Center, Weill Medical College of Cornell
University, New York, NY, USA
A liccia B ollig-Fischer D epartment of Oncology, Barbara Ann Karmanos Cancer
Institute, Wayne State University, D etroit, M I, U SA
P hilip T . C agle H ouston Methodist Hospital, Weill Medical College of Cornell
University, H ouston, T X, U SA
S hirish M . G adgeel K armanos Cancer Institute, Wayne State University, D etroit,
M I, U SA
M ary H elen Barcellos-Hoff D epartment of Radiation Oncology, New York
University School of Medicine, N ew York, N Y, U SA
S ajid H ussain N CI-designated Cancer Center, Sanford Burnham Prebys Medical
Discovery Institute, L a Jolla, C A, U SA
J ian-Yue J in C ancer Center, Georgia Regents University, A ugusta, G A, U SA
G regory P . K alemkerian Division of Hematology/Oncology, University of
Michigan, A nn Arbor, M I, U SA
F eng-Ming ( Spring) K ong C ancer Center, Georgia Regents University, Augusta,
GA, USA
K ristina M . K ruglyak O ncology, I llumina, Inc., S an Diego, C A, U SA
ix
