Role of Tumor Microenvironment in Breast Cancer and Targeted Therapies

Role of Tumor Microenvironment in Breast Cancer and Targeted Therapies
Copyright
Contributors
Preface
Introduction to various types of cancers
Introduction
Tissue homeostasis and the progression of cancer
Major types of cancer
Colorectal cancer
Risk factors
Lung cancer
Risk factors
Bladder cancer
Risk factors
Liver cancer
Main risk factors for liver carcinoma
Prostrate cancer (PCa)
Risk factors for prostate cancer
Breast cancer
Breast cancer pathogenesis
Risk factors for breast cancer
Summary
References
The tumor microenvironment
Introduction
The local microenvironment
The regional microenvironment
The metastatic microenvironment
Important players in the breast cancer immune microenvironment
Immunosuppressive cells
Myeloid-derived suppressor cells
Mast cells
M2-like tumor-associated macrophages
FoxP3+ regulatory T cells
Antitumor immune cells
Tumor-infiltrating T cells
Natural killer cells
Innate lymphoid cells
Dendritic cells
Eosinophils
Tumor microenvironment-targeting therapeutics
Summary
References
Role of cancer-associated fibroblasts in tumor microenvironment
Introduction
An overview of cancer-associated fibroblasts
Fibroblasts
Cancer-associated fibroblasts (CAFs)
Origin of cancer-associated fibroblasts
Biomarkers of CAFs
Heterogeneity of CAFs
Original heterogeneity
Phenotypic heterogeneity
Functional heterogeneity
CAFs activation mechanism
Role of CAFs
Tumor-promoting CAFs
Tumor-suppressive CAFs
CAF-immune microenvironment interaction in tumors
Interaction between CAFs and tumor-associated macrophages (TAMs)
CAFs and tumor-associated neutrophils (TANs)
CAFs and mast cells (MCs)
Targeting CAFs for clinical benefit
Challenges and directions
Conclusion
References
Role of mesenchymal stem cells in tumor microenvironment
Introduction
MSC phenotype and origin
Homing to the tumor microenvironment
Functions in the tumor microenvironment
MSCs exosomes therapy in tumors
MSC crosstalk with immune components of the inflammatory niche in solid cancer
MSCs and cells of the innate immune system
MSCs and cells of the adaptive immune system
Perinatal MSC as therapeutic strategy in cancer
Conclusion
References
Role of regulatory T cells in cancer
Introduction
Different subgroups of T regulatory cells
Naturally occurring CD4+ Tregs
Induced CD4+ T regulatory cells
CD8+ T regulatory cells, naturally occurring and induced
Immunosuppressive potential of T regulatory cells and cancer
T regulatory cell infiltration in tumor microenvironment
Regulatory T-cell antigen specificity in cancer
Role of regulatory T cells in cancer
Regulatory T cells in solid tumors
Regulatory T cells as biomarkers
T regulatory cells in hematologic malignancies
Cancer vaccines and regulatory T cells
Targeting T regulatory cells in cancer therapy
Depletion of T regulatory cells
Targeting function of regulatory T cells
Targeting the antioxidative ability of T regulatory cells
Regulation/modulation of T regulatory cell proliferation
Conclusion
References
Further reading
Role of tumor-associated macrophages in the breast tumor microenvironment
Introduction
Composition
Local microenvironment
Metastatic microenvironment
Macrophages in the tumor microenvironment
Recruitment of monocytes and macrophages to breast tumors
Differentiation and maturation of TAMs in breast tumors
Relative numbers of macrophages in breast cancer progression
Location of macrophages in breast tumors
TAMs and hypoxia
Hypoxia and macrophage recruitment
Hypoxia upregulates VEGF expression in TAMs
Hypoxia promotes immune evasion by TAMs
Hypoxic TAMs promote metastatic behavior of tumor cells
Breast cancer cell metastasis
Breast cancer angiogenesis
TAMs promote breast cancer cell stemness
TAMs modulate t-cell activity to induce an immunosuppressive microenvironment in breast cancer
TAMs regulate energy metabolism in breast cancer cells
Clinical significance of TAMs in breast tumors
Preclinical evidence for a role of TAMs in breast cancer treatment resistance
Chemotherapy
Radiotherapy
Anti-HER2-targeted therapy
Immunotherapy
Conclusion
References
Further reading
Role of Tumor-associated neutrophils in the breast tumor microenvironment
Introduction
Immunity and cancer
Cells associated with breast cancer
Neutrophils and cancer
Factors affecting recruitment of TANs into the tumor
Mechanism behind TANs
Various types of chemokines/cytokines acting as immunoeditors
Production of ROS by neutrophils is carcinogenic to humans
Proteolytic enzymes generated from leucocytes help malignancies in both matrix-independent as well as matrix-depen ...
Summary
References
The extracellular matrix in breast cancer
Introduction
The breast tissue's ECM architecture
ECM changes as breast cancer progresses
Rigidity of the ECM and tumor development
In morphological breast tumor subtypes, ECM dynamics are studied
The dynamics of the ECM in molecular breast tumor subtypes
Mechanosignaling changes
Immune system changes
Vasculature changes
ECM and metastasis
The initiation of the premetastatic niche is aided by ECM
ECM and the growth of tumors
Proliferation
Angiogenesis
Metastasis
Stromal remodeling is required for metastasis
Treatment resistance mediated by ECM
Limiting the entry of drugs
Resistance mediated through contact
Hypoxia and stemness levels are both on the rise
Dormancy induction
ECM remodeling as a result of treatment
The role of enzymes in ECM remodeling
The ECM of tumors can be targeted therapeutically
Conclusion
References
Breast cancer stem cells and their role in tumor microenvironment
Introduction
Origin of BCSCs
Breast cancer markers and targeted pathways involved in stem cell-mediated breast cancer progression
BCSCs and associated cellular markers
BCSCs and associated signaling pathways
Hedgehog signaling pathway
Wnt/β-catenin signaling pathway
PI3K/AKT/mTOR signaling pathway
Notch signaling pathway
BCSCs as a predictive marker
BCSC metabolism and tumor microenvironment
BCSCs targeting in therapy resistance and drug development
BCSCs: Current developments and therapeutic significance
Summary
References
Further reading
Targeting tumor microenvironment for breast cancer treatment
Introduction
Tumor microenvironment-A suitable target for treating breast cancer
The traditional cancer therapies and their interactions with the tumor microenvironment
Chemotherapy and tumor microenvironment
Chronic inflammation in the tumor microenvironment
Antiinflammatory drugs and breast cancer
Aspirin
Celecoxib
Therapies that aim at the TME
Radiotherapy and tumor microenvironment
Nanochemotherapeutics and tumor microenvironment
Targeting the extracellular matrix of TME
Targeting the CAFs of TME
Targeting the cancer stem cells of TME
Tumor microenvironment targeting by aiming at antiangiogenesis
Targeting exosomes of TME
Immediate immune system and tumor microenvironment
Hypoxia and acidosis in the tumor microenvironment
Summary
References
Index