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Bernhard Strauss - Rethinking Cancer: A New Paradigm for the Postgenomics Era

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Leading scientists argue for a new paradigm for cancer research, proposing a complex systems view of cancer supported by empirical evidence.Current consensus in cancer research explains cancer as a disease caused by specific mutations in certain genes. After dramatic advances in genome sequencing, never before have we known so much about the individual cancer cell--and yet never before has it been so unclear what to do with this knowledge. In this volume, leading researchers argue for a new theory framework for understanding and treating cancer. The contributors propose a complex systems view of cancer, presenting conceptual building blocks for a new research paradigm supported by empirical evidence.The contributors first discuss the new research framework in terms of theoretical foundations and then take up the relevance of a systems approach, reviewing such topics as nonlinearity, recurrence after treatment, the cellular attractor concept, network theory, and non-coding DNA--the dark matter of our genome. They address the temporality of cancer progression, drawing on evolutionary theory and clinical experience. Finally, they cover the dominant role of the tissue microenvironment in cancer, analyzing topics including altered metabolic pathways, the disease-defining influence on metastasis, and the interconnectedness of different environmental niches across levels of organization.

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Vienna Series in Theoretical Biology Gerd B Mller editor-in-chief Thomas - photo 1

Vienna Series in Theoretical Biology

Gerd B. Mller, editor-in-chief

Thomas Pradeu and Katrin Schfer, associate editors

The Evolution of Cognition, edited by Cecilia Heyes and Ludwig Huber, 2000

Origination of Organismal Form, edited by Gerd B. Mller and Stuart A. Newman, 2003

Environment, Development, and Evolution, edited by Brian K. Hall, Roy D. Pearson, and Gerd B. Mller, 2004

Evolution of Communication Systems, edited by D. Kimbrough Oller and Ulrike Griebel, 2004

Modularity: Understanding the Development and Evolution of Natural Complex Systems, edited by Werner Callebaut and Diego Rasskin-Gutman, 2005

Compositional Evolution: The Impact of Sex, Symbiosis, and Modularity on the Gradualist Framework of Evolution, by Richard A. Watson, 2006

Biological Emergences: Evolution by Natural Experiment, by Robert G. B. Reid, 2007

Modeling Biology: Structure, Behaviors, Evolution, edited by Manfred D. Laubichler and Gerd B. Mller, 2007

Evolution of Communicative Flexibility, edited by Kimbrough D. Oller and Ulrike Griebel, 2008

Functions in Biological and Artificial Worlds, edited by Ulrich Krohs and Peter Kroes, 2009

Cognitive Biology, edited by Luca Tommasi, Mary A. Peterson and Lynn Nadel, 2009

Innovation in Cultural Systems, edited by Michael J. OBrien and Stephen J. Shennan, 2009

The Major Transitions in Evolution Revisited, edited by Brett Calcott and Kim Sterelny, 2011

Transformations of Lamarckism, edited by Snait B. Gissis and Eva Jablonka, 2011

Convergent Evolution: Limited Forms Most Beautiful, by George McGhee, 2011

From Groups to Individuals, edited by Frdric Bouchard and Philippe Huneman, 2013

Developing Scaffolds in Evolution, Culture, and Cognition, edited by Linnda R. Caporael, James Griesemer, and William C. Wimsatt, 2013

Multicellularity: Origins and Evolution, edited by Karl J. Niklas and Stuart A. Newman, 2016

Vivarium: Experimental, Quantitative, and Theoretical Biology at Viennas Biologische Versuchsanstalt, edited by Gerd B. Mller, 2017

Landscapes of Collectivity in the Life Sciences, edited by Snait B. Gissis, Ehud Lamm, and Ayelet Shavit, 2017

Rethinking Human Evolution, edited by Jeffrey H. Schwartz, 2018

Convergent Evolution in Stone-Tool Technology, edited by Michael J. OBrien, Briggs Buchanan, and Metin I. Erin, 2018

Evolutionary Causation: Biological and Philosophical Reflections, edited by Tobias Uller and Kevin N. LaLand, 2019

Convergent Evolution on Earth: Lessons for the Search for Extraterrestrial Life, by George McGhee, 2019

Contingency and Convergence: Toward a Cosmic Biology of Body and Mind, by Russell Powell, 2020

Rethinking Cancer: A New Paradigm for the Postgenomics Era, edited by Bernhard Strauss, Marta Bertolaso, Ingemar Ernberg, and Mina J. Bissell, 2021

Rethinking Cancer

A New Paradigm for the Postgenomics Era

Edited by Bernhard Strauss, Marta Bertolaso, Ingemar Ernberg, and Mina J. Bissell

The MIT Press

Cambridge, Massachusetts

London, England

2021 Massachusetts Institute of Technology

All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means (including photocopying, recording, or information storage and retrieval) without permission in writing from the publisher.

Library of Congress Cataloging-in-Publication Data

Names: Strauss, Bernhard, editor. | Bertolaso, Marta, editor. | Ernberg, Ingemar, 1948- editor. | Bissell, Mina, editor.

Title: Rethinking cancer : a new paradigm for the postgenomics era / edited by Bernhard Strauss, Marta Bertolaso, Ingemar Ernberg, and Mina J. Bissell.

Other titles: Vienna series in theoretical biology.

Description: Cambridge, Massachusetts : The MIT Press, [2021] | Series: Vienna series in theoretical biology | Includes bibliographical references and index.

Identifiers: LCCN 2020029807 | ISBN 9780262045216 (hardcover)

Subjects: MESH: Neoplasms--genetics | Neoplasms--therapy

Classification: LCC RC268.4 | NLM QZ 210 | DDC 616.99/4042--dc23

LC record available at https://lccn.loc.gov/2020029807

Contents
  1. Gerd B. Mller, Thomas Pradeu, and Katrin Schfer
  2. Bernhard Strauss, Marta Bertolaso, Ingemar Ernberg, and Mina J. Bissell
  3. Bernhard Strauss
  4. Marta Bertolaso and Bernhard Strauss
  5. Thea Newman
  6. Sui Huang
  7. Ingemar Ernberg
  8. Peter Csermely
  9. Kahn Rhrissorrakrai and Laxmi Parida
  10. Jacob Scott, David Basanta, and Andriy Marusyk
  11. Kimberly J. Bussey and Paul C. W. Davies
  12. Larry Norton
  13. Roger Oria, Dhruv Thakar, and Valerie M. Weaver
  14. Maa dralevi and Jacques Pouyssgur
  15. Luca Vincenzo Cappelli, Liron Yoffe, and Giorgio Inghirami
  16. Courtney Knig and Christoph A. Klein
  17. Emmy W. Verschuren
  18. Bernhard Strauss, Marta Bertolaso, Ingemar Ernberg, and Mina J. Bissell

List of Figures

A representation of the hierarchy of systems for a glass of water and a human. The dashed line demarcates the subatomic hierarchy that is assumed for our purposes to be common to all systems considered.

A collection of images representing a small subset of the many behaviors of a system of water molecules: (a) the atomic structure of a water molecule and clockwise: (b) frost pattern on glass, (c) mackerel cloud, (d) cresting wave, (e) splash pattern, (f) Rayleigh-Bnard convection cells (from Getling1), and (g) fluid vortex.

The fluid packet as a mesoscale construct; a stepping-stone across the river of scales separating H2O molecules and the system-level behavior of water.

Some of the key mesoscale stepping-stones linking copper atoms to metallic conductivity in copper wire.

A mesoscale construct connecting the interactions of progenitor cancer and immune cells with the likelihood of subsequent clinical cancer presentation (cf. Palmer et al.17).

Formalizing the complex system for two levels: the cell (whose components are interacting genes) and the tumor tissue or cell population (whose components are the interacting cell types). The interacting components abstracted as black solid circles are the nodes (vertices) of a network in which the edges/arrows represent the interactions. The nodes are symbols that represent genes (or biomolecules) or cell types. They thus represent an ensemble of identical components (a named species of objects, such as a gene or a cell type), not individual components, and can take a value (abundance), represented by the variable x i for node i.

Basic concepts from dynamical systems theory applied to a gene regulatory network, GRN (for cell as a system), or to a cell-cell interaction network (tumor tissue as a system). For details, see text. (A) The fixed network architecture of a system of N = 9 components i = 1, 2, 3 N as an example of a network. (B) The configuration of xi activities of each network component (black dots) displayed as column. The entire configuration defines a state S and changes over time t, dictated by the interaction network. (C) Example of a configuration of the vector [x1, x2, x N ] as a bar graph for the values of x i at t1. (D) The N-dimensional state space (indicated by the nine coordinate axes). (E) Dimension reduction of the nine-dimensional state space to a two-dimensional XY-plane. (F) The quasi-potential landscape plotted by assigning each position ( = state

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