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Cancer Gene Networks

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Cover of 'Cancer Gene Networks'

Table of Contents

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    Book Overview
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    Chapter 1 Introduction: Cancer Gene Networks.
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    Chapter 2 Emerging Methods in Chemoproteomics with Relevance to Drug Discovery.
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    Chapter 3 ANXA7-GTPase as Tumor Suppressor: Mechanisms and Therapeutic Opportunities.
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    Chapter 4 Experimental and Study Design Considerations for Uncovering Oncometabolites.
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    Chapter 5 Targeting Deubiquitinating Enzymes and Autophagy in Cancer.
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    Chapter 6 Quantitative Clinical Imaging Methods for Monitoring Intratumoral Evolution.
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    Chapter 7 Transcriptome and Proteome Analyses of TNFAIP8 Knockdown Cancer Cells Reveal New Insights into Molecular Determinants of Cell Survival and Tumor Progression.
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    Chapter 8 Network-Oriented Approaches to Anticancer Drug Response.
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    Chapter 9 CRISPR/Cas-Mediated Knockin in Human Pluripotent Stem Cells.
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    Chapter 10 Complete Transcriptome RNA-Seq.
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    Chapter 11 Computational Methods and Correlation of Exon-skipping Events with Splicing, Transcription, and Epigenetic Factors.
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    Chapter 12 Tissue Engineering Platforms to Replicate the Tumor Microenvironment of Multiple Myeloma.
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    Chapter 13 microRNA Target Prediction.
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    Chapter 14 Evaluating the Delivery of Proteins to the Cytosol of Mammalian Cells.
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    Chapter 15 Validation of Biomarker Proteins Using Reverse Capture Protein Microarrays.
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    Chapter 16 Chemical Synthesis of Activity-Based Diubiquitin Probes.
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    Chapter 17 Profiling the Dual Enzymatic Activities of the Serine/Threonine Kinase IRE1α.
Attention for Chapter 6: Quantitative Clinical Imaging Methods for Monitoring Intratumoral Evolution.
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Chapter title
Quantitative Clinical Imaging Methods for Monitoring Intratumoral Evolution.
Chapter number 6
Book title
Cancer Gene Networks
Published in
Methods in molecular biology, January 2017
DOI 10.1007/978-1-4939-6539-7_6
Pubmed ID
Book ISBNs
978-1-4939-6537-3, 978-1-4939-6539-7

Joo Yeun Kim, Robert A. Gatenby, Kim, Joo Yeun, Gatenby, Robert A.


Usha Kasid, Robert Clarke


Solid tumors are multiscale, open, complex, dynamic systems: complex because they have many interacting components, dynamic because both the components and their interactions can change with time, and open because the tumor freely communicates with surrounding and even distant host tissue. Thus, it is not surprising that striking intratumoral variations are commonly observed in clinical imaging such as MRI and CT and that several recent studies found striking regional variations in the molecular properties of cancer cells from the same tumor. Interestingly, this spatial heterogeneity in molecular properties of tumor cells is typically ascribed to branching clonal evolution due to accumulating mutations while macroscopic variations observed in, for example, clinical MRI scans are usually viewed as functions of blood flow. The clinical significance of spatial heterogeneity has not been fully determined but there is a general consensus that the varying intratumoral landscape along with patient factors such as age, morbidity and lifestyle, contributes significantly to the often unpredictable response of individual patients within a disease cohort treated with the same standard-of-care therapy.Here we investigate the potential link between macroscopic tumor heterogeneity observed by clinical imaging and spatial variations in the observed molecular properties of cancer cells. We build on techniques developed in landscape ecology to link regional variations in the distribution of species with local environmental conditions that define their habitat. That is, we view each region of the tumor as a local ecosystem consisting of environmental conditions such as access to nutrients, oxygen, and means of waste clearance related to blood flow and the local population of tumor cells that both adapt to these conditions and, to some extent, change them through, for example, production of angiogenic factors. Furthermore, interactions among neighboring habitats can produce broader regional dynamics so that the internal diversity of tumors is the net result of complex multiscale somatic Darwinian interactions.Methods in landscape ecology harness Darwinian dynamics to link the environmental properties of a given region to the local populations which are assumed to represent maximally fit phenotypes within those conditions. Consider a common task of a landscape ecologist: defining the spatial distribution of species in a large region, e.g., in a satellite image. Clearly the most accurate approach requires a meter by meter survey of the multiple square kilometers in the region of interest. However, this is both impractical and potentially destructive. Instead, landscape ecology breaks the task into component parts relying on the Darwinian interdependence of environmental properties and fitness of specific species' phenotypic and genotypic properties. First, the satellite map is carefully analyzed to define the number and distribution of habitats. Then the species distribution in a representative sampling of each habitat is empirically determined. Ultimately, this permits sufficient bridging of spatial scales to accurately predict spatial distribution of plant and animal species within large regions.Currently, identifying intratumoral subpopulations requires detailed histological and molecular studies that are expensive and time consuming. Furthermore, this method is subject to sampling bias, is invasive for vital organs such as the brain, and inherently destructive precluding repeated assessments for monitoring post-treatment response and proteogenomic evolution. In contrast, modern cross-sectional imaging can interrogate the entire tumor noninvasively, allowing repeated analysis without disrupting the region of interest. In particular, magnetic resonance imaging (MRI) provides exceptional spatial resolution and generates signals that are unique to the molecular constituents of tissue. Here we propose that MRI scans may be the equivalent of satellite images in landscape ecology and, with appropriate application of Darwinian first principles and sophisticated image analytic methods, can be used to estimate regional variations in the molecular properties of cancer cells.We have initially examined this technique in glioblastoma, a malignant brain neoplasm which is morphologically complex and notorious for a fast progression from diagnosis to recurrence and death, making a suitable subject of noninvasive, rapidly repeated assessment of intratumoral evolution. Quantitative imaging analysis of routine clinical MRIs from glioblastoma has identified macroscopic morphologic characteristics which correlate with proteogenomics and prognosis. The key to the accurate detection and forecasting of intratumoral evolution using quantitative imaging analysis is likely to be in the understanding of the synergistic interactions between observable intratumoral subregions and the resulting tumor behavior.

Mendeley readers

The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 24 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 25%
Student > Ph. D. Student 4 17%
Student > Master 3 13%
Student > Bachelor 2 8%
Student > Doctoral Student 2 8%
Other 1 4%
Unknown 6 25%
Readers by discipline Count As %
Medicine and Dentistry 8 33%
Computer Science 2 8%
Neuroscience 2 8%
Biochemistry, Genetics and Molecular Biology 2 8%
Psychology 1 4%
Other 1 4%
Unknown 8 33%