From Molecular to Modular Tumor Therapy:: Tumors Are Reconstructible Communicatively Evolving Systems

ISBN-13: 9789400733237 / Angielski / Miękka / 2012 / 568 str.

Albrecht Reichle

Opis

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].

Spis treści

Introduction. 1.Bridging theory and therapeutic practice:From generalized disease models to particular patient. Part I; Therapy-derived systems biology: A pragmatic communication theory. 2. Tumor systems need to be rendered usable for a new action-theoretical abstraction:The starting point for novel therapeutic options. 3. Principles of modular tumor therapy. Part II; Tumors share common processes during tumor evolution:Communicative aspects of a situation’s interpretationfor creating systems-directed therapies. 4. Coagulation Cancer and Coagulation; focusing on tissue factor and heparanase. 5.The role of mesenchymal cells in cancer: contribution to tumor stroma and tumorigenic capacity. 6. Shaping Tumour Associated Macrophages: The Role of NF-?B. 7. The metabolic Achilles heel: tumor cell metabolism as therapeutic target. 8. Could be systems-directed therapy approaches promising in glioblastoma patients?. Part III; Systems-relevant molecular and cellular targets:Implementation of modular ‘knowledge’(Integration of communication). 9. Functional impacts of signal integration: Regulation of inflammation-related transcription factors by heterotrimeric G proteins. 10. Molecular cross-talk between nuclear receptors and nuclear factor-?B. 11. The biomodulatory capacities of low-dose metronomic chemotherapy: complex modulation of the tumor microenvironment. Part IV; Tumors are evolvable modular and rationalized systems:From molecular to modular tumor therapy. 12.Systems biology: A therapeutic target for tumor therapy. 13. The comparative uncovering of tumor systems biology by modularly targeting tumor-associated inflammation. 14. Searching for the ‘metabolism’ of evolution. Part V. Biomodulatory therapy approaches in metastatic cancer. 15. Therapeutic inflammation control may impact pathways ultimately determining outcome. 16. Cholangiocellular carcinoma. 17.A secretome-derived biomarker, C-reactive protein as response parameter to biomodulatory therapy inmetastatic renal clear cell carcinoma. 18. Modular therapy approach in metastatic castration-refractory prostate cancer. 19. Systems-directed therapy inmetastatic castration-refractory prostate cancer. Part VI; Criteria for checking systems behavior and creating predictions: Systems-associated biomarkers and molecular imaging. 20.Early detection of systems response: Molecular and functional imaging of angiogenesis. 21. The secretome, a novel tool of biomarkers for guiding biomodulatory therapy approaches. 22. Systems-associated prognostic biomarkers: A ‘late-stage’ biomarker. Part VII; harmacological considerations on systems biological therapy approaches. 23. Uncovering tumor systems biologyby biomodulatory therapy strategies. 24. Breathing new life into old drugs: Indication discovery by systems-directed therapy. Part VIII; Tumors’ systems biology: Implications for personalized therapy. 25.A methodologically guided approach for personalized therapy in metastatic cancer. Part IX; Summary. 26.From theme-dependent to evolution-adjusted tumor therapy.

Blurb

The traditional problem of the poor presentability as well as diagnostic and therapeutic practicability of individual patient care is still unresolved. The present book aims at leading the reader (cancer researchers, pharmacologists, biologists) away―in a scientifically accessible manner―from the daily conflicts between theory and practice and between the generalized and individual tumor patient, so that more personalized diagnostic and therapeutic strategies can be developed for controlling metastatic tumor disease: • First, recording the systems concept of tumor biology based on rather different sciences (biochemistry, cell biology, and medical oncology) including their potential contribution to communication, • then, giving reductionistically derived systems features an internal communicative context (formal-pragmatic communication theory), and • finally, binding the systems features to (tumor-immanent) evolutionary processes (modularity of biochemical and cellular processes, rationalization of biologic functions).