Clinical Efficacy of a Novel Therapeutic Principle, Anakoinosis

Heudobler, Daniel and Rechenmacher, Michael and Lueke, Florian and Vogelhuber, Martin and Klobuch, Sebastian and Thomas, Simone and Pukrop, Tobias and Hackl, Christina and Herr, Wolfgang and Ghibelli, Lina and Gerner, Christopher and Reichle, Albrecht (2018) Clinical Efficacy of a Novel Therapeutic Principle, Anakoinosis. FRONTIERS IN PHARMACOLOGY, 9: 1357. ISSN 1663-9812

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Abstract

Classic tumor therapy, consisting of cytotoxic agents and/or targeted therapy, has not overcome therapeutic limitations like poor risk genetic parameters, genetic heterogeneity at different metastatic sites or the problem of undruggable targets. Here we summarize data and trials principally following a completely different treatment concept tackling systems biologic processes: the principle of communicative reprogramming of tumor tissues, i.e., anakoinosis (ancient greek for communication), aims at establishing novel communicative behavior of tumor tissue, the hosting organ and organism via re-modeling gene expression, thus recovering differentiation, and apoptosis competence leading to cancer control - in contrast to an immediate, "poisoning" with maximal tolerable doses of targeted or cytotoxic therapies. Therefore, we introduce the term "Master modulators" for drugs or drug combinations 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., transcriptional modulators, metronomic low-dose chemotherapy, epigenetically modifying agents, protein binding pro-anakoinotic drugs, such as COX-2 inhibitors, IMiDs etc., or for example differentiation inducing therapies. Data on 97 anakoinosis inducing schedules indicate a favorable toxicity profile: The combined administration of master modulators, frequently (with poor or no monoactivity) may even induce continuous complete remission in refractory metastatic neoplasia, irrespectively of the tumor type. That means recessive components of the tumor, successively developing during tumor ontogenesis, are accessible by regulatory active drug combinations in a therapeutically meaningful way. Drug selection is now dependent on situative systems characteristics, to less extent histology dependent. To sum up, anakoinosis represents a new substantive therapy principle besides novel targeted therapies.

Item Type: Article
Uncontrolled Keywords: ACTIVATED RECEPTOR-GAMMA; RENAL-CELL CARCINOMA; PHASE-III TRIAL; LENALIDOMIDE PLUS DEXAMETHASONE; CHRONIC MYELOID-LEUKEMIA; HIGH-DOSE DEXAMETHASONE; TRANS-RETINOIC ACID; INTERFERON-ALPHA; BREAST-CANCER; METRONOMIC CHEMOTHERAPY; Anakoinosis; communicative reprogramming; transcriptional modulators; metronomic low-dose chemotherapy; glitazones; all-trans retinoic acid; COX-2 inhibitor; master modulators
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Depositing User: Petra Gürster
Date Deposited: 17 Jul 2020 09:54
Last Modified: 17 Jul 2020 09:54
URI: https://pred.uni-regensburg.de/id/eprint/13516

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