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Tumor Microenvironment
Dietmar W. Siemann (Edited by), DW Siemann (Author)
9780470749968, Wiley
Hardback, published 22 October 2010
464 pages
25 x 17.4 x 2.8 cm, 0.925 kg
"Overall, it would be useful to basic scientists interested in understanding the role of stroma, in particular the role of hypoxia, in cancer progression." (Doody's, 16 September 2011) "Tumor Microenvironment is informative and current. This field of study is already evolving beyond the microenvironment into the host systemic environment and the role of endocrine factors in tumor progression. If a second edition of the book is published, it will most certainly encompass these newly emerging concepts." (Elsevier, 2011)
The microenvironment in which a tumor originates plays a critical role in its initiation and progression. Tumor Microenvironment reviews the importance of tumor microenvironment in cancer management. Particular emphasis is placed on discussing how the unique characteristics of the tumor microenvironment not only impact disease progression and response to conventional anticancer therapies, but have also led to the identification of potential new therapeutic targets and treatment possibilities for cancer patients. Tumor Microenvironment also reviews the fundamental basis of target development, preclinical assessment, and the current clinical status of these therapies.
Preface xiii List of Contributors xv 1 The Microenvironment in Cancer 1 1.1 Introduction 1 1.2 A highly selective process is required to obtain the cancer phenotype 1 1.3 The cancer phenotype 2 1.4 The extracellular matrix 3 1.5 Motility, invasion, and metastatic ability 4 1.6 Impact of the tumor microenvironment on the control of cancer 4 1.7 Targeting the tumor microenvironment 5 1.8 Summary 5 References 6 2 Establishing the Tumor Microenvironment 7 2.1 Introduction 7 2.2 From cancerous cells to a tumor 8 2.3 A tumor is more than cancer cells and fibroblasts 9 2.4 Communication between the tumor cells and stroma 11 2.5 Hypoxia and angiogenesis 12 2.6 Conclusion 24 Acknowledgements 24 References 24 Further reading 33 3 Contributions of the Extracellular Matrix to Tumorigenesis 35 3.1 The extracellular matrix 35 3.2 Manipulation of the ECM during tumor development 38 3.3 Matricellular proteins and their complex effects on tumor development 39 3.4 Conclusion 47 References 48 4 Matrix Metalloproteinases and Their Inhibitors – Friend or Foe 53 4.1 Introduction 53 4.2 Matrix metalloproteinases 54 4.3 Tissue inhibitors of matrix metalloproteinases 63 4.4 Concluding comments 69 References 69 5 Role of Tumor-Associated Macrophages (TAM) in Cancer Related Inflammation 77 5.1 Introduction 77 5.2 Functional plasticity of macrophages 77 5.3 Macrophages as key orchestrators of cancer-related inflammation 79 5.4 Recruitment and differentiation of TAM 81 5.5 Protumoral functions of TAM 83 5.6 Molecular determinants of TAM functions 87 5.7 Therapeutic targeting of TAM 89 5.8 Conclusions 91 References 92 6 Bone Marrow Stroma and the Leukemic Microenvironment 99 6.1 Introduction 99 6.2 Components and function of the normal bone marrow microenvironment 99 6.3 Leukemia and its microenvironment 119 6.4 Summary 123 References 124 7 Microenvironment Factors Influencing Skeletal Metastases 135 7.1 Introduction 135 7.2 The bone microenvironment as a target for cancer cell dissemination 136 7.3 Roles of the bone microenvironment in promoting the arrest of circulating cancer cells at the skeleton 137 7.4 Concluding remarks 153 References 153 8 Premetastatic Niches 161 8.1 Introduction 161 8.2 ‘Seeds’ influencing the ‘Soil’ 162 8.3 Cellular components of premetastatic niches 164 8.4 ECM components of premetastatic niches 166 8.5 Premetastatic niche formation precedes metastatic growth 170 8.6 Therapeutic targeting of the premetastatic niche 172 8.7 Evidence for premetastatic niches in the clinic 174 8.8 Concluding remarks 174 References 175 9 Hypoxia, Anerobic Metabolism, and Interstitial Hypertension 183 9.1 Introduction 183 9.2 Pathophysiology of the tumor microenvironment 184 9.3 Evaluating the tumor microenvironment 189 9.4 Biologic and therapeutic implications 195 9.5 Clinical implications 199 9.6 Summary 201 References 201 10 Hypoxia and the DNA Damage Response 207 10.1 Introduction 207 10.2 The DNA damage response 208 10.3 Hypoxia regulation of DNA repair 215 10.4 Context synthetic lethality: exploiting hypoxic deregulation of DNA repair 220 10.5 Conclusions 221 References 221 11 Non-Invasive Imaging of the Tumor Microenvironment 229 11.1 Introduction 229 11.2 Imaging tumor vasculature, perfusion, and angiogenesis 229 11.3 Imaging tumor hypoxia: chronic and acute 234 11.4 Imaging tumor oxygen consumption 240 11.5 EPR oximetry 240 11.6 Imaging tumor interstitial fluid pressure (IFP) 244 11.7 Imaging tumor pH 245 11.8 Imaging tumor redox status 248 11.9 Imaging tumor response 250 11.10 Optimizing therapeutic intervention using molecular imaging 256 11.11 Conclusions 261 References 261 Further reading 270 12 Hypoxia-Inducible Factor 1 (HIF1) Mediated Adaptive Responses in the Solid Tumor 271 12.1 Introduction 271 12.2 Molecular consequences of tumor hypoxia 272 12.3 Hypoxia inducible factor 1 273 12.4 HIF-1 subunits and domain structure 273 12.5 Regulation of HIF-1α protein stability and activity by post-translational modifications 274 12.6 HIF isoforms 275 12.7 Oxygen-independent HIF signaling 276 12.8 HIF target genes 277 12.9 Hypoxia and oxygen delivery 279 12.10 Hypoxia and glucose metabolism 280 12.11 Hypoxia and acidosis 281 12.12 Hypoxia and metastasis 282 12.13 Therapeutic implications 283 References 285 13 Regulation of the Unfolded Protein Response in Cancer 291 13.1 Introduction 291 13.2 The UPR signaling cascade 292 13.3 Hypoxia activates UPR 295 13.4 UPR and expression of UPR-targeted genes in cancer 298 13.5 Concluding remarks 304 References 304 14 Influence of Hypoxia on Metastatic Spread 311 14.1 Introduction 311 14.2 The metastatic process 313 14.3 The tumor microenvironment and metastasis 316 14.4 Summary 326 References 326 15 Drug Penetration and Therapeutic Resistance 329 15.1 Introduction 329 15.2 Tumor microenvironment 330 15.3 Drug penetration 334 15.4 In vitro tumor models 338 15.5 Conclusions 346 References 347 16 Impact on Radiotherapy 353 16.1 Introduction 353 16.2 The tumour vasculature and microenvironment 353 16.3 Influence of tumor hypoxia on radiation therapy 356 16.4 Reducing hypoxia by increasing oxygen delivery 358 16.5 Radiosensitizing hypoxic cells 363 16.6 Killing the resistant cell population 365 16.7 Vascular targeting approaches 366 16.8 Conclusions and future perspectives 367 References 368 17 HIF-1 Inhibitors for Cancer Therapy 377 17.1 Introduction 377 17.2 Small molecule inhibitors of HIF- 1 378 17.3 Exploiting HIF-1 inhibitors in combination strategies 391 17.4 Conclusions 392 Acknowledgements 392 References 393 18 Vascular-Targeted Molecular Therapy 401 18.1 Introduction 401 18.2 Approaches to targeting tumor vasculature in vivo 403 18.3 Alternative targeting strategies 412 18.4 Concluding remarks 413 Acknowledgements 413 References 413 Index 421
Nicole N. Parker and Dietmar W. Siemann
Allison S. Betof and Mark W. Dewhirst
Marie Schluterman Burdine and Rolf A. Brekken
Mumtaz V. Rojiani, Marzenna Wiranowska and Amyn M. Rojiani
Antonio Sica and Chiara Porta
William B. Slayton and Zhongbo Hu
Alessandro Fatatis, Julia A. D’Ambrosio, Whitney L. Jamieson, Danielle L. Jernigan and Mike R. Russell
Kevin L. Bennewith, Janine T. Erler and Amato J. Giaccia
Michael F. Milosevic
Isabel M. Pires, Rachel Poole and Ester M. Hammond
Bénédicte F. Jordan and Bernard Gallez
Tereza Goliasova and Nicholas C. Denko
Jing Zhang and Albert C. Koong
Richard P. Hill and Naz Chaudary
Andrew I. Minchinton and Alastair H. Kyle
Michael R. Horsman, Jens Overgaard and Dietmar W. Siemann
Annamaria Rapisarda and Giovanni Melillo
Graeme J. Dougherty and Shona T. Dougherty
Subject Areas: Biology, life sciences [PS]
