From Molecular to Modular Tumor Therapy:: Tumors are Reconstructible Communicatively Evolving Systems(3 The Tumor Microenvironment)

Chronic inflammation is one of the major pathological bases manifesting the development of gastric cancers, hepatitis and hepatocellular carcinoma, cervical cancer, ulcerative colitis and colorectal cancer [1]. Microbial infections, viral infections and autoimmune responses can lead to chronic inflammation-associated cancer formation. Human herpesviruses, such as human cytomegalovirus (HCMV) and Kaposi sarcoma herpesvirus (KSHV) are known to be associated with tumorigenesis and tumor progression. HCMV infection potentiates malignancies of colon cancer and malignant glioma [2,3]. KSHV was initially discovered from Kaposi's sarcoma lesion of an AIDS patient [4]. It was subsequently discovered that KSHV contributed to the pathogenesis of KS, primary effusion lymphoma [5] and lymphoproliferative disorder multicentric Castleman's disease. Emerging evidence shows that herpesvirus infection interferes or inhibits host cell immune defense and maintains a tumor-promoting microenvironment by expressing virulent homologues of host cell proteins that disturb normal cell cycle progression and leads to apoptosis of the host cells. For example, cellular growth and transformation are induced by viral-encoded homologues of cytokines, chemokines or chemokine receptors [6]. The constitutive expression of viral chemokine GPCRs triggers prolonged activation of G protein signaling and eventually becomes the major inputs for chronic leukocyte infiltration and cancer development. GPCRs can serve as proto-oncogenes since overexpression of various wild type GPCRs can transform cells in the presence of their specific ligands. Mutations on GPCRs may result in constitutive signaling and oncogenesis [7]. Naturally occurring mutations in GPCRs have been identified in human tumors [8,9].

Table of Contents:
Therapy-Derived Systems Biology: A Pragmatic Communication Theory.- Bridging Theory and Therapeutic Practice: From Generalized Disease Models to Particular Patients.- Tumor Systems Need to be Rendered Usable for a New Action-Theoretical Abstraction: The Starting Point for Novel Therapeutic Options.- Principles of Modular Tumor Therapy.- Tumors Share Common Processes During Tumor Evolution: Communicative Aspects of a Situation’s Interpretation for Creating Systems-Directed Therapies.- Cancer and Coagulation; Focusing on Tissue Factor and Heparanase.- The Role of Mesenchymal Cells in Cancer: Contribution to Tumor Stroma and Tumorigenic Capacity.- Shaping Tumor Associated Macrophages: The Role of NF-?B.- The Metabolic Achilles Heel: Tumor Cell Metabolism as Therapeutic Target.- Could Be Systems-Directed Therapy Approaches Promising in Glioblastoma Patients?.- Systems-Relevant Molecular and Cellular Targets: Implementation of Modular ‘Knowledge’.- Functional Impacts of Signal Integration: Regulation of Inflammation-Related Transcription Factors by Heterotrimeric G Proteins.- Molecular Cross-Talk Between Nuclear Receptors and Nuclear Factor-?B.- The Biomodulatory Capacities of Low-Dose Metronomic Chemotherapy: Complex Modulation of the Tumor Microenvironment.- Tumors are Evolvable Modular and Rationalized Systems: From Molecular to Modular Tumor Therapy.- Systems Biology: A Therapeutic Target for Tumor Therapy.- The Comparative Uncovering of Tumor Systems Biology by Modularly Targeting Tumor-Associated Inflammation.- Searching for the ‘Metabolism’ of Evolution.- Biomodulatory Therapy Approaches in Metastatic Cancer.- The Impact of Inflammation Control and Active Cancer Palliation on Metabolic Pathways Determining Tumor Progression and Patient Survival.-Pioglitazone and Rofecoxib Combined with Angiostatically Scheduled Capecitabine in Far-Advanced Hepatobiliary Carcinoma.- C-Reactive Protein As a Secretome-Derived Biomarker for Predicting Response to Biomodulatory Therapy in Metastatic Renal Clear Cell Carcinoma.- Modular Therapy Approach in Metastatic Castration-Resistent Prostate Cancer.- Systems-Directed Therapy in Metastatic Castration-Resistent Prostate Cancer (CRCP).- Criteria for Checking Systems Behavior and Creating Predictions: Systems-Associated Biomarkers and Molecular Imaging.- Early Detection of Systems Response: Molecular and Functional Imaging of Angiogenesis.- Secretome Proteomics, a Novel Tool for Biomarkers Discovery and for Guiding Biomodulatory Therapy Approaches.- Cyclooxygenase 2 (COX2) and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Are Stage-Dependent Prognostic Markers of Malignant Melanoma.- Pharmacological Considerations on Systems Biological Therapy Approaches.- Uncovering Tumor Systems Biology by Biomodulatory Therapy Strategies.- Breathing New Life into Old Drugs: Indication Discovery by Systems Directed Therapy.- Tumors’ Systems Biology: Implications for Personalized Therapy.- A Methodological Approach to Personalized Therapies in Metastatic Cancer.- Summary.- To Be an Object in a Biological System.- From Molecular to Modular, from Theme-Dependent to Evolution-Adjusted Tumor Therapy.