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Int. J. Mol. Sci. 2018, 19(11), 3540; https://doi.org/10.3390/ijms19113540

Peroxisome Proliferator-Activated Receptors (PPAR)γ Agonists as Master Modulators of Tumor Tissue

1
Department of Internal Medicine III, University Hospital Regensburg, Hematology and Oncology, 93042 Regensburg, Germany
2
Department Biology, Universita’ di Roma Tor Vergata, 00173 Rome, Italy
3
Institut for Analytical Chemistry, Faculty Chemistry, University Vienna, Vienna A-1090, Austria
*
Author to whom correspondence should be addressed.
Received: 28 September 2018 / Revised: 27 October 2018 / Accepted: 6 November 2018 / Published: 9 November 2018
(This article belongs to the Special Issue PPARs in Cellular and Whole Body Energy Metabolism)
PDF [504 KB, uploaded 9 November 2018]

Abstract

In most clinical trials, thiazolidinediones do not show any relevant anti-cancer activity when used as mono-therapy. Clinical inefficacy contrasts ambiguous pre-clinical data either favoring anti-tumor activity or tumor promotion. However, if thiazolidinediones are combined with additional regulatory active drugs, so-called ‘master modulators’ of tumors, i.e., transcriptional modulators, metronomic low-dose chemotherapy, epigenetically modifying agents, protein binding pro-anakoinotic drugs, such as COX-2 inhibitors, IMiDs, etc., the results indicate clinically relevant communicative reprogramming of tumor tissues, i.e., anakoinosis, meaning ‘communication’ in ancient Greek. The concerted activity of master modulators may multifaceted diversify palliative care or even induce continuous complete remission in refractory metastatic tumor disease and hematologic neoplasia by establishing novel communicative behavior of tumor tissue, the hosting organ, and organism. Re-modulation of gene expression, for example, the up-regulation of tumor suppressor genes, may recover differentiation, apoptosis competence, and leads to cancer control—in contrast to an immediate, ‘poisoning’ with maximal tolerable doses of targeted/cytotoxic therapies. The key for uncovering the therapeutic potential of Peroxisome proliferator-activated receptor γ (PPARγ) agonists is selecting the appropriate combination of master modulators for inducing anakoinosis: Now, anakoinosis is trend setting by establishing a novel therapeutic pillar while overcoming classic obstacles of targeted therapies, such as therapy resistance and (molecular-)genetic tumor heterogeneity.
Keywords: anakoinosis; communicative reprogramming; nuclear transcription factors; metronomic low-dose chemotherapy; glitazones; all-trans retinoic acid; COX-2 inhibitor; master modulators; undruggable targets; therapy pillar; peroxisome proliferator-activated receptors (PPARs), energy homeostasis; metabolic regulations; organ cross-talk; cancer and reprogramming of energy metabolism; systems biology anakoinosis; communicative reprogramming; nuclear transcription factors; metronomic low-dose chemotherapy; glitazones; all-trans retinoic acid; COX-2 inhibitor; master modulators; undruggable targets; therapy pillar; peroxisome proliferator-activated receptors (PPARs), energy homeostasis; metabolic regulations; organ cross-talk; cancer and reprogramming of energy metabolism; systems biology
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Heudobler, D.; Rechenmacher, M.; Lüke, F.; Vogelhuber, M.; Pukrop, T.; Herr, W.; Ghibelli, L.; Gerner, C.; Reichle, A. Peroxisome Proliferator-Activated Receptors (PPAR)γ Agonists as Master Modulators of Tumor Tissue. Int. J. Mol. Sci. 2018, 19, 3540.

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