Peroxisome Proliferator-Activated Receptors (PPAR)γ Agonists as Master Modulators of Tumor Tissue.
Daniel HeudoblerMichael RechenmacherFlorian LükeMartin VogelhuberTobias PukropWolfgang HerrLina GhibelliChristopher GernerAlbrecht ReichlePublished in: International journal of molecular sciences (2018)
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.
Keyphrases
- gene expression
- small molecule
- low dose
- palliative care
- clinical trial
- randomized controlled trial
- metabolic syndrome
- small cell lung cancer
- squamous cell carcinoma
- magnetic resonance imaging
- dna methylation
- insulin resistance
- stem cells
- advanced cancer
- mesenchymal stem cells
- machine learning
- systemic lupus erythematosus
- single molecule
- binding protein
- young adults
- locally advanced
- cell proliferation
- long noncoding rna
- oxidative stress
- heart rate
- bioinformatics analysis
- phase ii
- childhood cancer
- double blind
- heat shock protein