Peroxisome proliferator-activated receptors (PPAR)γ agonists as master modulators of tumor tissue
Heudobler D, Rechenmacher M, Lueke F, Vogelhuber M, Pukrop T, Herr W, Ghibelli L, Gerner C, Reichle A (2018)
Publication Type: Journal article, Review article
Publication year: 2018
Journal
Book Volume: 19
Article Number: 3540
Journal Issue: 11
DOI: 10.3390/ijms19113540
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.
Involved external institutions
Universitätsklinikum Regensburg
Germany (DE)
Universität Wien / University of Vienna
Austria (AT)
Università degli Studi di Roma 'Tor Vergata'
Italy (IT)
Germany (DE)
Universität Wien / University of Vienna
Austria (AT)
Università degli Studi di Roma 'Tor Vergata'
Italy (IT)
How to cite
APA:
Heudobler, D., Rechenmacher, M., Lueke, F., Vogelhuber, M., Pukrop, T., Herr, W.,... Reichle, A. (2018). Peroxisome proliferator-activated receptors (PPAR)γ agonists as master modulators of tumor tissue. International Journal of Molecular Sciences, 19(11). https://doi.org/10.3390/ijms19113540
MLA:
Heudobler, Daniel, et al. "Peroxisome proliferator-activated receptors (PPAR)γ agonists as master modulators of tumor tissue." International Journal of Molecular Sciences 19.11 (2018).
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