Table Of ContentCancer Systems Biology, Bioinformatics
and Medicine
Alfredo Cesario • Frederick B. Marcus
Editors
Cancer Systems Biology,
Bioinformatics and Medicine
Research and Clinical Applications
1 3
Editors
Dr. Alfredo Cesario Dr. Frederick B. Marcus
IRCCS San Raffaele Pisana Advanced Therapies and Systems Medicine
Scientific Direction Health Research Directorate
Via di Valcannuta 247 European Commission
00166 Rome, Italy and Brussels, Belgium
Department of Surgery [email protected]
Catholic University [email protected]
Largo Agostino Gemelli, 1
00166 Rome, Italy
[email protected]
[email protected]
ISBN 978-94-007-1566-0 e-ISBN 978-94-007-1567-7
DOI 10.1007/978-94-007-1567-7
Springer Dordrecht Heidelberg London New York
Library of Congress Control Number: 2011933914
© Springer Science+Business Media B.V. 2011
The contents of this book are based upon referenced, publicly available sources, specifically books,
publications and websites and on the contributions of the chapter authors. Although at the time of pub-
lication, one editor (FBM) is an employee of the European Commission, this book is their work alone
and it is not sponsored by the Commission, nor is it a Commission publication. The editors and authors
are not receiving any royalties on this book. The contents may not in any circumstances be regarded as
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Springer is part of Springer Science+Business Media (www.springer.com)
.
We dedicate this book to all those suffering
from cancer, and to their families, carers,
nurses and physicians.
.
Preface
Nature of This Book
This book is a comprehensive and integrated textbook about systems approaches to
cancer biology, bioinformatics and medicine, aimed at students, researchers and cli-
nicians, that documents and builds upon many of the most recent advances in cancer
science, technology, diagnosis, treatment and analysis methods. These approaches are
applied to central processes in cancer origins and progression, and to translational ap-
plications including cancer diagnosis, drug development and treatment. The methods
involve at least some level of computational analysis involving multiple interactions
which are quantified, classified, analysed and modelled for optimized description.
New genomic and proteomic measurements and cancerous phenotypes are causally
linked (or capable of being so) at the molecular, cellular and tissue levels; research
is directly and functionally connected with outcomes, using clinical observations
as immediate feedback and input. Computational models of primary and secondary
networks at the molecular and physiological levels can serve as test beds for devel-
oping and testing new biomarkers, drugs and treatment strategies, and enhance the
efficiency, coherency and economy of the pre-clinical test phase and clinical trials.
These approaches transform fragmented investigations into integrated pipelines
of research, discovery, monitoring and treatment, based on a quantitative under-
standing of various cancer mechanisms and their behaviour. Systems approaches
thereby energize translational research, where fundamental knowledge of key pro-
cesses is applied to clinical practice and personalized medicine.
Authors, Level of Presentation and Readership
Many of the 48 authors from 11 countries are world-renowned scientists, clinicians
and organizational leaders in their fields, some of which they founded. Their chap-
ters contain comprehensive presentations, pragmatic tools, guidance and inspiration
for transforming cancer research and therapy, together with thousands of experi-
mental, computational and clinical references.
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vviiiiii Preface
The book is designed as a textbook for graduate students in their first and sec-
ond year of PhD or MD studies and sufficiently advanced undergraduates in life
sciences, biomedical and medical studies. It is also a comprehensive reference and
survey for professional researchers of cancer systems approaches. Readers with-
out a mathematical background can still benefit from most of the contents, which
will allow them to understand the field, and to work closely with computational
experts. In fact, independently of the systems aspects, a state-of-the-art descrip-
tion is provided of cancer as a multi-faceted disease, along with relevant research,
diagnosis and treatment, so computational biologists will gain the biological and
clinical background necessary for effectively working in cancer research. Doctors,
clinicians, and university and industrial researchers will find essential references for
their investigations and new directions in therapies.
Organisation and Contents
The book has a logically-developed, integrated and cross-referenced presentation,
and contains (by chapters):
Part I—Introduction and Background
1. An overview of the topics covered in the book with a general introduction to the
basis of systems biology, bioinformatics, and medicine approaches.
2. The morphology and pathology of the full range of cancers, including their grade
and stage, plus the most prevalent cancers, their specific sub-classifications,
implications for treatment, and the need to move to a systems context.
Part II—Laboratory, Clinical, Data and Educational Resources
3. Major advances in genomic and proteomic measurement technologies and their
application to cancer research in the context of numerical modelling.
4. Cellular and tissue material essential for cancer research, model organisms and
their modifications, and means of making optimum choices for elucidating bio-
logical function in cancer.
5. A wide range of genomic sequence and expression databases which form the
basis of systems research in cancerous processes, and some major collaborative
efforts in data generation.
6. Interdisciplinary skills for researchers and doctors, along with the educational
processes and infrastructures that support basic investigations and clinical
applications.
Part III—Bioinformatics and Systems Biology Analysis
7. A comprehensive description of the mathematical basis for systems approaches
and their areas of application.
8. A guide to the wide range of computational tools and databases available and
how to access and use them optimally.
Preface iixx
9. Cancer progression in a systems context via modelling methods, demonstrating
the power of these techniques.
10. Cellular pathways of cell-death processes and their relation to various cancer
progression modes and interactions with therapies, also illustrating the benefits
of collaborative and interdisciplinary research.
11. The utilization of gene expression data and biological motifs for diagnosis and
analysis of tumour growth.
12. Evolutionary paradigms used to examine novel systems approaches to under-
standing tumour growth and reaction in the presence to treatment and bodily
defences.
Part IV—Diagnosis and Treatment Applications
13. Biomarker development for diagnosis, prognosis and drug development, and
their identification and correct interpretation to aid therapy.
14. Systems approaches for improving productivity and understanding at several
stages in the drug development process, with examples of their use by the phar-
maceutical industry.
15. Cancer chronotherapy and choices of combination therapies, dosage and tim-
ing, improving treatment outcomes during clinical trials, and computational
frameworks for optimization of these choices.
16. An overview and synthesis of systems approaches to biomarkers, drug develop-
ment and therapies, together with new directions concerning their application
to clinical trials.
17. The role of robustness in understanding cancer as a systems disease, resistance
to therapy, and new treatment paradigms.
Part V—Perspectives and Conclusions
18. Near and medium term prospects for advances in systems applications, and
areas for progress, especially the application of synthetic biology technologies.
19. Conclusions from each chapter, integrated themes found in the book, and ave-
nues for clinical practice.
Description:This teaching monograph on systems approaches to cancer research and clinical applications provides a unique synthesis, by world-class scientists and doctors, of laboratory, computational, and clinical methods, thereby establishing the foundations for major advances not possible with current methods
