Anakoinosis for Promoting Tumor Tissue Editing: Novel Therapeutic Opportunities for Establishing Clinically Relevant Tumor Control by Targeting Tumor Plasticity

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Background

In contrast to the suggested predominance of genetic aberrations as main drivers of tumor behavior, communication processes among cell compartments in tumor tissues equally appreciate cell autonomous and cell non-autonomous systems functions, i.e., structures and functions constituted at the edge of heterotypic cell systems and include the tissue of tumor harboring organs. Therapeutically modified communication within tumor tissues places special emphasis on homeostasis maintaining processes, the adjustment of hubs, the amazing diversity of communication techniques of cell systems, the sensing, and the context-dependent interpretation of signals .



Regulatorily active drug combinations for the treatment of refractory metastatic tumor disease uncovered that therapeutically guided communication processes in tumor tissues, so called pro-anakoinotic approaches, may ‘edit’ tumor tissues by exploiting tumor cell and tissue plasticity, thereby establishing biologic hallmarks facilitating attenuation of tumor growth or induction of continuous complete remission. Tumor cell or tissue plasticity may be considered as the ability of cell compartments in cancer tissues to dramatically change their phenotypes without additional genetic mutations in response to environmental, including therapeutic requirements.



Anakoinosis, meaning communicative reprogramming, brings to attention that tumor evolution is no one-way trait, and that endogenous communication protocols promoting tumor growth, may be therapeutically turned into protocols supporting clinically beneficial biologic hallmarks, such as differentiation, transdifferentiation, immunosurveillance, or alternative ways to cell death. Moreover, the fact that communication protocols can be therapeutically redeemed to integrate novel homeostatic, ‘normalized’ conditions, indicates that normal functioning communication lines can be reactivated in tumor tissues.



The recruitment of a broad diversity of communicatively involved sites in tumor tissues, beyond those directly triggered by genetic aberrations, opens huge treatment advantages: Refractory disease may respond at primary and metastatic tumor sites, and quite different histologic tumor types are therapeutically accessible by similar pro-anakoinotic therapy schedules.



Here, modern tumor pathophysiology could step in,

• evaluating therapy-guided tumor systems stages, such as differentiation, transdifferentiation, immunosurveillance, or alternative ways of tumor cell death,

• studying possibilities for repurposing targeted therapies, i.e., composition of pro-anakoinotic drug combinations, and providing novel target patterns for approved drugs following tumor tissue editing,

• applying multifold therapeutic technologies for tumor tissue editing on the background of the broad diversity of communication techniques operated by tumor tissues and the accessibility of tumor-associated communication protocols for pro-anakoinotic drug combinations,

• and considering structural and functional tissue re-organizations following preceding tumor therapies, for appropriately adapting up-coming systemic tumor therapies in case of tumor progression or relapse.



The Research Topic covers an interdisciplinary field including biologic, medical, and pharmacologic aspects and will consider original research with translational, pre-clinical and clinical studies, as well as review papers. The topic will address a very broad readership as basic considerations on tumor pathophysiology are up for discussion to expand therapeutic opportunities for long-term metastatic tumor control.

Keywords: molecular tissue dynamics, cancer microenvironment, communicative reprogramming, non-cytotoxic anticancer therapy, sustainable drug development

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