Bone Cancer

Bone Sarcomas and Bone Metastases - From Bench to Bedside

3rd Edition - September 22, 2021
Editor: Dominique Heymann
Language: English
Hardback ISBN:
9 7 8 - 0 - 1 2 - 8 2 1 6 6 6 - 8
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 8 9 9 9 0 - 1

Bone Cancer: Bone Sarcomas and Bone Metastases - From Bench to Bedside, Third Edition comprehensively investigates key discoveries in the field of bone biology. New aspects o… Read more

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Bone Cancer: Bone Sarcomas and Bone Metastases - From Bench to Bedside, Third Edition comprehensively investigates key discoveries in the field of bone biology. New aspects of bone cancer biology are treated in new chapters covering exosomes, autophagy, and metabolism. These have led to the development of entirely new areas for investigation, such as therapies which combine surgery and biological approaches.

The Third Edition expands on the original overview of bone cancer development (physiology and pathophysiology), with 40% new material. Each chapter has been written by internationally recognized specialists on the bone cancer microenvironment, bone metastases, osteoclast biology in bone cancer, proteomics, bone niche, circulating tumor cells, and clinical trials.

Given the global prevalence of breast and prostate cancers, knowledge of bone biology has become essential for everyone within the medical and cancer research communities. Bone Cancer: Bone Sarcomas and Bone Metastases - From Bench to Bedside continues to offer the only translational reference to cover all aspects of primary bone cancer and bone metastases. This revision opens the door to myeloma with two short chapters dedicated to this bone-associated disease.

Cover image
Title page
Table of Contents
Copyright
Contributors
Foreword I
Foreword II
Foreword III
Preface
Basic Aspects of Bone Cancers
Section I. Epidemiology of Bone Cancers
Chapter 1. Cancer: lessons to learn from the past
Introduction
Who studies cancer(s) in ancient people(s)?
How do we recognize cancer in the past?
What do we know about the past of cancer? a global perspective
Limits and pitfalls of paleo-oncology
Conclusion and perspectives
Chapter 2. Epidemiology of primary bone tumors and economical aspects of bone metastases
Incidence of primary bone tumors
Age
Gender
Site distribution
Incidence of bone tumors as a secondary event
Racial differences in incidence of primary bone tumors
Incidence of bone metastases
Pathology of bone metastases
Cost of illness
Economic burden of bone metastasis
Conclusions
Section II. Animal Models of Bone Cancers
Chapter 3. Mammalian models of bone sarcomas
Introduction
Models based on the inoculation of cancer cells and the implantation of tumor fragments
Genetically engineered animal models
Conclusion
Chapter 4. In vivo models used in studies of bone metastases
Introduction
Models used in the studies of breast cancer bone metastases (Table 4.1)
In vivo models of prostate cancer bone metastases (Table 4.2)
Modeling metastasis to/in human bone (Table 4.3)
Murine models of myeloma-induced bone disease (Table 4.4)
Conclusions
Chapter 5. Zebrafish models for studying bone tumors
Advantages of zebrafish models for cancer research
Osteochondroma
Ewing sarcoma
Osteosarcoma
Section III. Machine Learning and Artificial Intelligence
Chapter 6. Use of machine learning in bone cancers
Introduction
Machine learning models in bone cancer
Conclusions and perspectives
Chapter 7. Artificial intelligence for bone cancer imaging
Introduction
AI technologies
AI-assisted tumor detection and segmentation
Tumor characterization
Image processing
Using AI to guide patient management
Conclusion
Section IV. Preparation of Tissue Samples
Chapter 8. Technical aspects: how do we best prepare bone samples for proper histological analysis?
Introduction
Bone biopsy in humans or large animals
Bone fixation
Micro–computed tomography
Dehydration and infiltration of bone samples
Bone embedding
Staining methods
Section V. Bone Microenvironment and Bone Cancer
Chapter 9. Bone niche and bone metastases
Introduction
Normal bone homeostasis and the unique bone microenvironment
Functions of the metastatic niches
Bone microenvironment as metastatic niches
Conclusions and perspectives
Chapter 10. Bone, a fertile soil for tumor development
Introduction
Osteotropism
Outgrowth of metastatic tumors in bone
The vicious cycle of bone metastases
Influence of resident bone cell populations on tumor growth
Concluding remarks
Chapter 11. Osteomimicry: old concepts and new findings
Introduction
Osteoblast biology
Osteoblast contribution in the vicious cycle
Osteomimicry: key milestones
New modulators of osteomimicry
Tumor-induced osteomimicry
Conclusions and perspectives
Chapter 12. The role of mesenchymal stem cells in bone cancer: initiation, propagation, and metastasis
Introduction to the mesenchymal stem cell
Initiation: MSCs as progenitors of bone tumors
Propagation: cancer stem cells in bone sarcoma
Metastasis: MSCs prepare the road for metastasis
Conclusion
Chapter 13. Technical approaches for studying the communications between osteocytes and cancer cells
Introduction
In vitro approaches
In vivo approaches
Conclusion
Section VI. Dialog Between Cancer Cells and Bone Cells
Chapter 14. Osteocytes and bone tumor niche
Introduction
Osteocytes: a multifunctional bone cell
The central role of osteocytes in bone remodeling through RANK/RANKL and Wnt pathways
Deregulation of RANK/RANKL and Wnt pathways in malignancy
Is there a direct link between malignant cells and osteocytes?
Conclusions and perspectives
Chapter 15. Immune functions of osteoclasts: new insights for bone cancers
Introduction
Osteoclasts are members of the innate immune system
The innate immune function of OCLs
Immunosuppressive function of OCLs and its consequences in osteolytic tumors
Conclusion
Chapter 16. The immune environment of bone sarcomas
Introduction
Implication of immune environment in bone sarcoma's progression
Chondrosarcoma's immune environment
Tumor-associated macrophages and CHS progression
Dedifferentiated CHS
ICP and CHS progression
Chordoma's immune environment
Immunotherapies for bone sarcomas
Conclusion
Chapter 17. Macrophages and pathophysiology of bone cancers
Introduction
Macrophage differentiation, polarization, and activation status
Tumor-associated macrophages
Metabolic regulation of TAMs
Macrophages in cancer cell intravasation and extravasation
Macrophages in metastasis
Macrophages in breast cancer bone metastasis
Macrophages in prostate cancer bone metastasis
Macrophages in osteosarcoma
Therapeutic interests of macrophages in bone cancer
Conclusions and perspectives
Section VII. Mediators of Cell Communications
Chapter 18. Growth factors, cytokines, and pediatric malignant primary bones tumors
Introduction
TGF-β family implications in pediatric malignant primary bone tumors
FGF family implications in pediatric malignant primary bone tumors
WNT family implications in pediatric malignant primary bone tumors
HH family implications in pediatric malignant primary bone tumors
IL-6 family implications in pediatric malignant primary bone tumors
Conclusions and perspectives
Chapter 19. Effects of NF-κB manipulation on cancer-associated bone disease
Introduction
Role of NF-κB on bone metastasis
Role of NF-κB on primary bone cancer
Conclusions and perspectives
Chapter 20. Transforming growth factor-β and its signaling pathway in skeletal complications of malignancy
Introduction
The life of TGF-β, from synthesis to the TGF-β signaling pathway
TGF-β during bone development and maintenance
TGF-β in early-stage cancer and primary cancer of the bone
TGF-β in secondary cancer of the bone or bone metastases from solid tumors
Conclusion and perspectives
Chapter 21. Extracellular vesicles, tumor growth, and the metastatic process
Introduction
Extracellular vesicles
Extracellular vesicle cargo and cancer
Extracellular vesicles and tumor growth
Extracellular vesicles and the tumor microenvironment
Extracellular vesicles and metastasis
Potential biomarkers and anti-tumor therapy
Conclusions and perspectives
Chapter 22. Connexin43 and development of primary bone tumors: osteosarcoma and Ewing's sarcoma
Gap junction channels
Role of gap junctions in bone remodeling
Connexin43 in primary bone cancers
Conclusion and perspectives
Chapter 23. Role of classical cannabinoid receptors in cancer-associated bone disease
Introduction
Role of the endocannabinoid system in bone metastasis
Role of the endocannabinoid system in primary bone cancer
Conclusion and future direction
Chapter 24. Impact of the acid microenvironment on bone cancers
Introduction
Source of acidosis in the bone cancer microenvironment
Effect of acidosis on cancer cells
Effect of acidosis on tumor-associated stroma
Acid-related cancer-induced bone pain
Targeting acidosis in bone
Conclusion
Section VIII. Metabolism
Chapter 25. Hypoxia-inducible factor (HIF)–mediated effects of the hypoxic niche in bone cancer
Introduction
Hypoxia-inducible factor
Bone cancer
Conclusions and perspectives
Chapter 26. Energy metabolism in bone tumors: fuel selection and adaptation
Introduction
Imaging of cellular energy metabolism in osseous metastatic disease
Metabolites contribution to the fertile soil for bone lesions development
Energetic reprogramming genes in osteo-oncology
Treatments targeting tumor cells energetic metabolism in bone
Conclusions and perspectives
Section IX. Cell Plasticity and Tumor Heterogeneity
Chapter 27. EMT process in bone metastasis
Introduction
EMT in physiological processes and cancer
EMT in the primary tumor and metastatic dissemination
EMT and metastasis to the bone
EMT and cancer stem cells
EMT, circulating tumor cells, and disseminated tumor cells in the bone marrow
MET and outgrowth of metastasis
Bone marrow–derived cells in EMT and MET regulation
Therapeutic targets in bone metastasis and EMT
Perspective
Chapter 28. Cancer stem cells and clonal evolution in bone sarcomas
Introduction
Identification of CSCs in bone sarcomas
Stemness signaling in osteosarcoma
Metastatic signaling and stemness in osteosarcoma
Clonal evolution of bone sarcomas
Conclusions and perspectives
Chapter 29. Dormancy in cancer bone metastasis
Introduction
Cellular and tumor mass dormancy
Factors influencing dormancy
Models of tumor dormancy
Remaining questions and future directions
Conclusion
Section X. Biomarkers
Chapter 30. Bone remodeling markers and bone cancer
Introduction
Diagnostic use
Prognostic use
Monitoring of antitumor therapy
Conclusions and perspectives
Chapter 31. Epigenetic heterogeneity in primary bone cancers
Introduction
The human epigenetic landscape
Epigenetic heterogeneity in primary bone cancers
Epigenetic heterogeneity in primary bone cancers: from bench to bedside
Conclusion
Chapter 32. MicroRNA implication in therapeutic resistance and metastatic dissemination of bone-associated tumors
Introduction
MicroRNAs implication in metastatic dissemination of bone-associated tumors
MicroRNAs and chemoresistance
Chapter 33. MicroRNAs and bone metastasis: how small RNAs regulate secondary tumor formation and progression in the skeleton
Introduction
MicroRNAs: from biogenesis to biological functions
MicroRNAs regulate multiple steps of bone metastasis formation and progression
MicroRNAs as prognostic biomarkers
Concluding remarks
Chapter 34. Long noncoding RNA and bone sarcoma
Introduction
Biogenesis, classification, and function of lncRNA
Expression and function of lncRNAs in osteosarcoma
lncRNAs in other bone sarcomas
Conclusions
Chapter 35. Liquid biopsy in bone sarcomas and identification of new biomarkers
Bone sarcoma malignancies: origin, treatment, and diagnosis
Current and potential bone sarcoma biomarkers
Osteosarcoma, Ewing sarcoma, and chondrosarcoma: current status of liquid biopsies
Conclusion and future perspectives
Chapter 36. Disseminated tumor cells in bone marrow of cancer patients: biology and clinical relevance
Introduction
Biology of DTCs
Clinical relevance of DTCs in the bone marrow
Conclusions
Primary Bone Tumors
Section XI. Biological Aspects
Chapter 37. Cytogenetics of bone tumors
Introduction
Cartilage tumors
Osteogenic tumors
Fibrogenic tumors
Fibrohistiocytic tumors
Ewing's sarcoma/primitive neuroectodermal tumor
Giant cell tumor
Notochordal tumors
Vascular tumors
Myogenic, lipogenic, neuronal, and epithelial tumors
Tumors of undefined neoplastic nature
Conclusion
Chapter 38. Genetic aspects of primary bone tumors
Introduction
Cartilaginous neoplasms
Bone-forming tumors
Conclusion and perspectives
Chapter 39. Markers for bone sarcomas
Introduction
Preliminary consideration
Markers of osteogenic sarcomas
Markers for chondrogenic sarcomas
Markers in Ewing's sarcoma and other round cell tumors
Markers in other primary bone sarcomas
Conclusion
Chapter 40. Molecular pathology of osteosarcoma
Introduction
Genomic instability and genetic changes
Tumor suppressor gene dysfunction in osteosarcoma
Oncogenes in osteosarcoma
RECQ helicases
microRNA involvement
Genes involved in osteosarcoma metastasis
Molecular insights into therapeutics
Conclusion
Chapter 41. Genomic and proteomic profiling of osteosarcoma
Introduction
Genetic and chromosome alterations
Predisposing germline mutations
Altered signaling pathways
Developmental pathways altered in OS
Markers of disease progression
Markers derived from proteomics
Other markers influencing OS phenotype
Conclusions and future perspectives
Chapter 42. Ewing's sarcoma family of tumors
Introduction
Clinical features and pathogenesis
Diagnosis and staging
Treatment
Conclusion
Chapter 43. Molecular aspects of Ewing's sarcomas
Introduction
Ewing's sarcoma oncogenes
The cell of origin of Ewing's sarcoma
Other genetic events
Roles of FET-ETS fusions
Interaction with microenvironment
Understanding metastatic disease
Conclusion
Chapter 44. Osteoclast-rich lesions of bone: a clinical and molecular overview
Osteoclast-rich neoplasms of bone
The cherubism phenotype: cherubism, Noonan-like/multiple giant cell lesion of the jaw, and neurofibromatosis
Conclusion
Chapter 45. Biology of cartilage tumor family
Introduction
Benign cartilage tumors
Malignant cartilage tumors
Conclusion and perspectives
Section XII. Imaging
Chapter 46. Imaging of bone sarcomas
Introduction
Imaging techniques
Imaging characteristics and considerations of specific sarcoma types
Chordoma
Adamantinoma
Conclusion
Section XIII. Therapeutic Approaches
Chapter 47. Current therapeutic approaches of bone sarcomas
Introduction
Surgery
Computer-assisted navigation
Chemotherapy
Radiation therapy
Therapeutic approaches for primary metastatic and recurrent disease
Follow-up
Cancer rehabilitation
Chapter 48. What is an adequate margin after bone tumor resection?
Introduction
Margins, a mainstay in bone tumor management
Characterization of margins
What is an adequate margin?
Conclusion
Chapter 49. Regulated cell death and drug resistance in malignant bone tumors
Introduction
Osteosarcoma
RCD in Ewing's sarcoma
RCD in chondrosarcoma
Conclusion and perspective
Chapter 50. Chondrosarcoma of bone: diagnosis and therapy
Introduction
Classification
Difficulties in making the diagnosis of chondrosarcoma
Therapy and prognosis
Perspective of new therapeutic approaches
Conclusion
Chapter 51. Radiation therapy for primary bone tumors
Introduction
Radiobiology of bone tumors
Radiation therapy techniques
Ewing's sarcoma
Osteosarcoma
Chondrosarcoma
Chordoma
Giant cell tumor of bone
Li–Fraumeni syndrome and primary bone tumors
Follow-up and long-term toxicities
Conclusion
Chapter 52. New therapeutic advances of bone sarcomas
Introduction
Conclusion
Bone Metastases
Section XIV. Biological Aspects
Chapter 53. The histopathology of skeletal metastases
Introduction
Treatment and prevention of bone metastases
Biology of bone metastases
Bone metastases
Several primary tumors with a predilection for skeletal metastasis
Metastatic carcinoma of unknown primary site
Conclusion
Chapter 54. Identification of new therapeutic targets of bone cancers by proteomic strategies
Introduction
Bone homeostasis and cancer
Current treatments for tumors originating within bone and bone metastatic cancers
Proteomic methods within biomarker discovery
Taking proteomic targets toward the clinic
Summary
Section XV. Clinical Aspects and Imaging
Chapter 55. Interventional radiologic techniques in the management of bone tumors
Introduction
Image-guided bone biopsy
Therapeutic embolization
Bone tumor ablation
Vertebral augmentation
Conclusions and perspectives
Chapter 56. Diagnosis of bone metastases in urological malignancies—an update
Introduction
History and examination
Serum and bone markers for bone metastases
Imaging modalities
Positron emission tomography/computed tomography
Fluciclovine PET/CT
Urological malignancies—recommendations
Conclusion
Section XVI. Bone Pain
Chapter 57. Mechanisms and management of bone cancer pain
Introduction
Mechanisms of bone cancer pain
Therapeutic strategies
Conclusions and perspectives
Chapter 58. Involvement of sympathetic nerves in bone metastasis
Introduction
The “vicious” cycle of bone destruction
What primes the vicious cycle?
Chronic stress reduces survival rate in patients with breast cancer
Influence of sympathetic nerves on the bone microenvironment
Effect of chronic stress on bone metastasis
β-blockers for the prevention of breast cancer metastasis
Implications for other types of solid and blood cancers
Chapter 59. Pain control with palliative radiotherapy in patients with bone metastases
Introduction
Principles of palliative radiation therapy
Mechanism of action in relief of painful bone metastases
Pain monitoring
Assessment of quality of life
Local field radiation therapy: clinical evidence
Wide-field radiation therapy: clinical evidence
Side effects of local field radiotherapy
Side effects of wide-field radiotherapy
Postoperative radiotherapy
Complications of bone metastases
Reirradiation
Cost-effectiveness
Other treatment modalities and their integration with external beam radiotherapy
Perspectives and conclusions
Chapter 60. Palliative care for patients with bone metastases
The definition of palliative care
Incidence
Pathophysiology
Diagnostic imaging
Clinical, biochemical, and radiological manifestations
Treatment: general considerations
Impact on patient quality of life
Section XVII. Therapeutic Approaches
Chapter 61. Role of radiation therapy in patients with bone metastasis
Introduction
Mechanisms of action of radiation therapy in bone metastasis
The purposes of radiation therapy
Indications
Dose and fractionation of RT
Side effects
Re-irradiation
Stereotactic body radiotherapy
Other treatment modalities and their integration with external beam radiotherapy
Conclusion
Chapter 62. Cellular and molecular actions of bisphosphonates
Introduction
Simple BPs are converted to toxic metabolites
Nitrogen-containing BPs inhibit FPP synthase
N-BPs prevent the prenylation of small GTPase proteins
Inhibition of FPP synthase causes accumulation of IPP and the formation of ApppI
Activation of Vγ9Vδ2T cells by IPP
Detecting the pharmacological effects of N-BP the mevalonate pathway
Effects of BP on bone cells other than osteoclasts
Conclusions and perspectives
Chapter 63. Bone-targeted agents and skeletal-related events in breast cancer patients with bone metastases
Introduction
Incidence
Diagnosis and types of bone metastases
Response to treatment in bone metastases
Predicting bone metastases
Pathophysiology of bone metastases
Treatment of bone metastases
Denosumab
Clinical trials and use of bisphosphonates and bone-active agents in breast cancer
Some problems
Chapter 64. Bone metastases—current status of bone-targeted treatments
Multidisciplinary management of bone metastases
Bone-targeted agents in oncology
Prevention of skeletal morbidity in metastatic bone disease
Practical recommendations on use of bone-targeted agents in advanced cancer patients
Safety aspects
Prevention of bone metastases
Future considerations
Conclusions
Chapter 65. Therapies of bone metastases in castration-resistant prostate cancer
Introduction
Pathophysiology and preclinical advances
Clinical complications and treatments
Conclusions
Chapter 66. Targeted radionuclide therapy in bone cancer
Intended figures
Introduction
Theranostic bone-seeking radionuclide therapies
Bone-seeking radionuclide therapies
Prostate cancer
Osteosarcoma
Future prospects
Chapter 67. The effects of anticancer therapies on bone metastases in breast cancer
Introduction
Current systemic therapies for breast cancer bone metastases
Mechanisms of action
Emerging clinical trials on new therapeutic approaches for bone metastases in breast cancer
Conclusions and perspectives
Part IV. Myeloma: A Bone Associated Disease
Chapter 68. Biological relationship between bone and myeloma cells
Introduction
Myeloma-induced bone disease
Multiple myeloma causes an increase in osteoclast-activating factors
Multiple myeloma inhibits osteoblast formation and differentiation
Conclusions and perspectives
Chapter 69. Recent therapeutic approaches in myeloma
Introduction
Overview of treatment approaches in multiple myeloma
Bone disease
Pathophysiology of myeloma bone disease
Therapeutic approaches for myeloma-related bone disease
Conclusions and perspectives
Index

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Bone Cancer

Bone Sarcomas and Bone Metastases - From Bench to Bedside

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Dominique Heymann