Role of Tumor Microenvironment in Breast Cancer and Targeted Therapies

Role of Tumor Microenvironment in Breast Cancer and Targeted Therapies
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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