Table Of ContentMolecular
Targeted Therapy
of Lung Cancer
Yuichi Takiguchi
Editor
123
Molecular Targeted Therapy of Lung Cancer
Yuichi Takiguchi
Editor
Molecular Targeted Therapy
of Lung Cancer
Editor
Yuichi Takiguchi
Department of Medical Oncology
Graduate School of Medicine
Chiba University
Chiba, Japan
ISBN 978-981-10-2000-1 ISBN 978-981-10-2002-5 (eBook)
DOI 10.1007/978-981-10-2002-5
Library of Congress Control Number: 2017930607
© Springer Science+Business Media Singapore 2017
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Preface
In 2004, a randomized study involving patients with advanced non-small cell lung
cancer (NSCLC) demonstrated a 1.7 months’ benefit in median overall survival
time (OS) with the combination chemotherapy consisting of docetaxel and cisplatin
(median OS of 11.3 months) over the combination chemotherapy consisting of vin-
desine and cisplatin (median OS of 9.6 months) [1]. Although this study changed
the 20-year standing standard of care for patients with advanced NSCLC that was
established at 1981 [2], the survival time advantage was very small. From that time
up to now, however, by adding an antiangiogenesis agent to the standard combina-
tion chemotherapy [3], by including newer agents [4, 5], and by incorporating main-
tenance therapy [6], a small advantage in each landmark study had steadily
accumulated up to 16.9 months of median OS [6], which was almost twice long
compared to the one with vindesine plus cisplatin. Although limited to patients with
cancer harboring particular driver mutations, drastic prolongation of median OS has
been observed by incorporating molecular-target agents [7–9]. Further improve-
ment in prolonging OS is expected by incorporating newly developed immune
checkpoint therapy [10, 11]. The advancement in the treatment for advanced
NSCLC in the latest decade has been accompanied by advancement of technologies
for molecular-marker detection and in bioinformatics. It has also involved issues of
regulatory science and companion diagnostics. Because of the large patient number
available and existence of definitive driver oncogenes, the recent clinical study on
advanced NSCLC has led the recent clinical studies of many other cancers.
The current topics on treatment of lung cancer, its related translational research,
and regulatory science are discussed in this book. Future directions especially
focusing on the epithelial-to-mesenchymal transition, cancer stem-cell nature, and
the interaction between cancer and its microenvironment are also discussed.
The editor and most of the authors are the faculty members of the integrated and
interuniversity educational organization “International Training Program for
Co-operative Experts in Clinical Oncology” of “the Cultivation Plan for Cancer
Care Professionals (Gann Pro)” (http://kanto-kokusai-ganpro.md.tsukuba.ac.jp)
consisting of Chiba University, Tsukuba University, Gunma University, Nippon
Medical School, Saitama Medical School, and Dokkyo Medical School. Besides
v
vi Preface
expecting wide-ranging readership, we also provide the book with a role as a text-
book for graduated students participating in this program.
The authors are hoping that further development in lung cancer treatment will
further relieve the pain of patients and families.
Chiba, Japan Yuichi Takiguchi
References
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Contents
Part I Diagnosis
1 Classification of Adenocarcinoma of the Lung, with
a Special Reference to Prognosis ........................................................... 3
Yukio Nakatani, Yoko Yonemori, Jun Matsushima,
and Takuya Yazawa
2 Screening Lung Cancer with Low-Dose CT Combined
with Molecular Markers ......................................................................... 29
Yuichi Takiguchi
3 PET-CT, Bio-imaging for Predicting Prognosis and Response
to Chemotherapy in Patients with Lung Cancer ................................. 45
Kyoichi Kaira
4 Methods in Molecular Diagnosis ........................................................... 63
Koichi Hagiwara
5 Accurate Nodal Staging and Biomarker Testing
with Endobronchial Ultrasound- Guided Transbronchial
Needle Aspiration .................................................................................... 79
Takahiro Nakajima and Ichiro Yoshino
6 Next-Generation Sequencing and Bioinformatics ................................ 97
Reika Kawabata-Iwakawa, Hidemasa Bono,
and Masahiko Nishiyama
7 Companion Diagnostics .......................................................................... 117
Emi Noguchi
Part II Treatment
8 Small Cell Lung Cancer and Molecular Targeted Therapy ................ 139
Shunichiro Iwasawa
ix
x Contents
9 Locally Advanced Non-small Cell Lung
Cancer and Targeted Therapy ............................................................... 155
Ikuo Sekine
10 EGFR Mutant .......................................................................................... 167
Kunihiko Kobayashi and Hiroshi Kagamu
11 ALK Mutant ............................................................................................ 191
Akihiko Gemma
12 Minor-Driver Mutant ............................................................................. 199
Akihiko Miyanaga
13 Mechanism of Resistance to Targeted Molecular Therapy ................. 213
Masahiro Seike
14 Immunotherapy ....................................................................................... 227
Takahiro Ebata
15 Lung Cancer Complicated with Interstitial Lung Diseases ................ 239
Yuji Minegishi
16 Management of Adverse Effects by Molecular
Targeted Therapy and Immunotherapy ............................................... 253
Toshimichi Miya
Part III Evaluation
17 Health-Related Quality of Life in Molecular Targeted Therapy ........ 271
Shinji Nakamichi and Kaoru Kubota
18 Gene Signature ........................................................................................ 279
Hideki Ujiie, Daiyoon Lee, Tatsuya Kato, and Kazuhiro Yasufuku
Part IV Novel Approach
19 Targeting Epithelial-Mesenchymal Transition and Cancer
Stem Cell .................................................................................................. 295
Ryota Kurimoto and Yuichi Takiguchi
20 Targeting the Lung Cancer Microenvironment:
Harnessing Host Responses .................................................................... 309
Mark M. Fuster
Part I
Diagnosis
