Research Topic

Tumor Systems Biology: How To Therapeutically Redirect Dysregulated Homeostasis in Tumor Systems (i.e. Anakoinosis)

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Classic tumor therapies that consist of cytotoxic agents and/or targeted therapies have failed to overcome therapeutic limitations such as tumor-associated high-risk genetic parameters, genetic heterogeneity at different metastatic sites or undruggable targets. An alternative treatment strategy, based on the ...

Classic tumor therapies that consist of cytotoxic agents and/or targeted therapies have failed to overcome therapeutic limitations such as tumor-associated high-risk genetic parameters, genetic heterogeneity at different metastatic sites or undruggable targets. An alternative treatment strategy, based on the principle of communicative reprogramming of tumor tissues, i.e. anakoinosis, aims at establishing novel communicative behavior of tumor tissue in the hosting organ and organism.

The current therapeutic focus is inducing multi-level biologic effects and systems by re-modeling gene expression, thus recovering differentiation and apoptosis ability, leading to cancer control, in contrast to an immediate, ‘poisoning’ with maximally tolerable doses of targeted or cytotoxic therapies. Trials with pro-anakoinotic activity profile, thus, follow a completely different treatment concept, tackling biologic processes and systems. Dysregulated homeostatic pathways or dysregulated transcriptional networks in tumors are now a major target for combined therapies aimed at communicative reprogramming tumor tissues, thereby recalling patterns of evolutionary processes provided by single cell types and cell systems in a tumor.

The challenge in the treatment of incurable cancer types is to understand complex network of regulatory pathways in terms of tissue and organ-specific cell communication, aiming to modulate regulatory circuitries. Due to the dependency of pro-anakoinotic processes on tumor- and stage-dependent communicative networks, the effects of anakoinotic treatments are dependent on the cellular context and the tumor-bearing organ.

We introduced the term ‘master modulators’ for drugs promoting evolutionary processes or regulating homeostatic pathways. These ‘master modulators’ comprise a broad diversity of drugs, characterized by the capacity for reprogramming tumor tissues, i.e. drugs acting as transcriptional modulators, epigenetic modifiers, differentiating agents, inhibitors of modulatory proteins such as COX-2, IMiDs, immunomodulators, often administered as metronomic therapy, like metronomic chemotherapy, etc. But also, drugs ‘normalizing’ the microbiome for enhancing the efficacy of anti-tumor therapy should be numbered along with biomodulatory drugs with multi-level activity profiles.

Combined administration of master modulators (frequently with poor or no mono activity) may even induce continuous complete remission in refractory metastatic neoplasia, irrespectively of the tumor type. Drug selection is now dependent on systems characteristics, not necessarily histology dependent: single combinatory schedules of master modulators are cross-responsive among quite different tumor histologies and this clearly indicates that different tumor histologies share identical patterns of hallmarks of cancer and constitute similar physical organizations of hallmarks, so-called rationalizations of hallmarks, despite underlying (molecular-) genetic tumor heterogeneity.

This Research Topic welcomes Reviews, Mini-Reviews and Original Research that cover the singular and intricate homeostatic pathways and dysregulated transcriptional networks in cancer and hematologic neoplasia, which may be accessible for targeted regulatory active therapy with ‘master modulators’. This novel research topic is an evolution and advancement of a preceding research topic recently published in Frontiers in Pharmacology (ANAKOINOSIS - Re-Establishing Apoptosis Competence via Communicative Reprogramming: A Novel Anticancer Therapy). This collection includes, but is not limited to:

REGULATORY CIRCUITRIES IN TUMOR TISSUE:
• Dysregulation of transcriptional networks in tumors
• Dysregulated tumor suppressor genes and tumor phenotype
• Cell-autonomous and non-autonomous defense mechanisms against oncogene mutation and phenotypic tumor transformation
• Apoptosis, caspases, and regeneration in injured normal and cancer tissues: a concern in anticancer therapies

REGULATORY HOMEOSTATIC MECHANISMS IN EPITHELIAL TISSUES:
• Regulation of cell stemness
• Stem cells in organ regeneration
• Homeostasis in healthy and cancer tissues
• Mechanism of deranged tissue homeostasis control

ROLE OF IMMUNE INFILTRATES IN CANCER TISSUE HOMEOSTASIS:
• Remodeling immune response to tumors
• Immune response in the primary tumor and metastatic sites

IMAGE ANALYSIS AND COMPUTATIONAL MODELS FOR TUMOR GROWTH AND TUMOR RESPONSE TO THERAPY:
• Image analysis and microfluidic devices for tumor growth and tumor response to therapy
• Computational models of tumor growth and anakoinosis

MICROBIOME AS REGULATOR OF CANCER HOMEOSTASIS:
• Microbiome and impact on graft versus host disease
• Microbiome and tumor response to therapy

CLINICAL APPROACHES TO CANCER-ORGANISM CROSSTALK:
• Tumor-associated cachexia
• Serum proteome and lipidome during developing tumor disease

ANAKOINOSIS: THERAPEUTIC CROSSTALK WITH SYSTEMS BIOLOGICAL PROCESSES:
• Communication-theoretical considerations
• Communication-technical instruments


Keywords: Anakoinosis, homeostatic pathways, immune infiltrates and cancer homeostasis, therapeutic cross talk with systems biology, cancer-organism-cross talks, microbiome as regulator of tissue homeostasis, image analysis and computational models


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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18 June 2019 Manuscript

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18 June 2019 Manuscript

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