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

摘要: 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 or tumor promotion. However, if 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 such COX-2 inhibitors, IMiDs, etc., the results indicate clinically communicative reprogramming tissues, anakoinosis, meaning ‘communication’ in ancient Greek. The concerted master modulators may multifaceted diversify palliative care even induce continuous complete remission refractory metastatic disease and hematologic neoplasia by establishing novel behavior tissue, hosting organ, organism. Re-modulation gene expression, for example, up-regulation suppressor genes, recover differentiation, apoptosis competence, leads to cancer control—in contrast an immediate, ‘poisoning’ maximal tolerable doses targeted/cytotoxic therapies. key uncovering therapeutic potential Peroxisome proliferator-activated receptor γ (PPARγ) agonists is selecting appropriate combination inducing anakoinosis: Now, anakoinosis trend setting a pillar while overcoming classic obstacles targeted therapies, therapy resistance (molecular-)genetic heterogeneity.