|
| References | Nuclear receptor | Treatment | Clinical phase | Number of patients | Human tumors or cell types | Main conclusions of the authors |
|
| Liposarcoma |
| Demetri et al., 1999 [148] | PPARγ | Troglitazone (per os, 1 × 800 mg/d, 6 weeks) | Phase II | 3 | High-grade liposarcomas | Induction of cell differentiation in a human solid tumors |
| Debrock et al., 2003 [149] | PPARγ | rosiglitazone (4 mg/d for 1 year) | Phase II | 12 | Liposarcoma | Increased PPARγ activity: no correlation with clinical outcome |
|
| Prostate cancer |
| Mueller et al., 2000 [150] | PPARγ | Troglitazone (per os, 2 × 400 mg/d, 12 weeks) | Phase II | 41 | Human prostate cancer | Prolonged stabilization of PSA with PSA close to 0 in 1 patient |
| Paltoo et al., 2003 [151] | PPARγ Pro12Ala |
Impact of a gene polymorphism on prostate cancer development | 193 (versus 188 controls) | Prostate cancer | No association of prostate cancer and Pro12Ala polymorphism |
| Xu et al., 2003 [152] | PPARγ | Tosiglitazone | Preclinical | Primary culture of human prostatic cancer cells | Prodifferentiating properties of thiazolidinediones |
| Dawson and Slovin, 2003 [153] | Vit D PPARγ | Review | Prostate cancers | |
| Smith et al., 2004 [154] | PPARγ | Rosiglitazone 2 × 4 mg/d 338 d (versus placebo 315 d) | Phase II | 105 | Prostate carcinoma without recent hormone therapy and with a rise in PSA after radical prostatectomy and/or radiation without metastasis | No advantage over placebo efficacy and PPARγ do not contribute to prostate cancer development |
| Saif et al., 2009 [155] | PPARγ agonist and LTB4 receptor antagonist | LY29311 (in combination with gemcitabine) | Phase II | 67 (combined therapy) versus 66 (gemcitabine alone) | Advanced pancreatic carcinoma | No benefit obtained by adding LY293111 to gemcitabine |
|
| Colo-rectal cancer |
| Kulke et al., 2002 [156] | PPARγ | Troglitazone per os | Phase II | 25 | Chemoresistant colorectal metastatic cancer | No objective tumor response |
| Choi et al., 2008 [157] | PPARγ | 15d-PGJ2 pioglitazone | Preclinical | APC-mutated HT-29 human colon cancer cells | PPARγ ligand promotes growth of APC-muted HT-29 colon cancer cells |
| Dai and Wang, 2010 [158] | PPARγ | Review | Colorectal cancer | Mechanisms by which PPARγ impacts carcinogenesis in colorectal cancer |
| Tenenbaum et al., 2008 [159] | All PPARs | Panagonist bezafibrate retard 400 mg/d | Bezafibrate Infarctus Prevention (BIP) study | 3011 with coronary artery disease and no cancer | 1506 given bezafibrate 1505 given placebo | Experimental support for preventive effects of bezafibrate towards colon cancer |
| Breast cancer |
| Burstein et al., 2003 [160] | PPARγ | Troglitazone 800 mg/d for 6 months | Phase II | 22 | Breast cancer refractory to one chemotherapy or two hormonal therapies | Little apparent clinical effect in patients with treatment refractory metastatic breast cancer |
| Faddy et al., 2006 [161] | | | Preclinical | | (1) ER dependence of PPARα
(2) PPARα levels = marker of breast cancer cell resistance to histone deacylase inhibitors |
| Zaytseva et al., 2008 [162] | PPARγ1 | RNAi | Preclinical | MCF-7 breast cancer cells | PPARγ1 signaling impacts balance between proliferation and apoptosis towards proliferation in breast cancer |
|
| Leukemia |
| Hasegawa et al., 2007 [163] | PPARγ | Fuligocondis B via increase in PGJ2 | Preclinical | Leukemia cells | 15d-PGJ2 sensitizes TRAIL-resistant cells to TRAIL independent on PPARγ |
| Tsao et al., 2010 [164] | PPARγ | 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) 15d-PGJ2 | Preclinical Phase I | 9 | Acute myelogenous leukemia cell lines from 9 patients | PPARγ regulates apoptosis via activation of caspase 8 and co-activator DRIP205 promotes cell differentiation by PPARγ |
|
| Thyroid cancer |
| Kebebew et al., 2006 [165] | PPARγ | Rosiglitazone 4 mg/d 1 week + 8 mg/d 7 weeks | Phase II | 10 patients | Differentiated thyroid cancer | Rosiglitazone may induce radioiodine uptake in some patients possibly via PPARγ-independent pathways |
| Tepmongkol et al., 2008 [166] | PPARγ | Rosiglitazone 8 mg/d for 6 weeks | Phase II | 23 | Thyroid carcinoma | Increase of radioiodine uptake in thyroid tumors possibly via PPARγ-independent mechanisms |
|
| Glioma and glioblastoma, lung cancer |
| Yao et al., 2006 [167] | HMG-CoA reductase PPARγ | Lovastatin + troglitazone | Preclinical | Glioblastoma and lung cancer cell lines | Induction of P27 [Kip 1] (statines), E2F-1 (glitazone), + CDK2, cyclin A. Rb phosphorylation status |
| Hau et al., 2008 [168] | COX-2 inhibitors PPARγ | Rofecoxib pioglitazole in association with low-dose chemotherapy | Phase II | 44 | High-grade gliomas (glioblastomas or anaplastic glioma) | Moderate activity encouraging future utilization in highly selected patients |
|
| Head and neck cancer |
| Schweitzer et al., 2010 [169] | PPARγ | Review | Head and neck cancers | Therapeutic use of PPARγ ligands in head and neck cancer |
|
| Melanoma |
| Botton et al., 2009 [170] | PPARγ | Ciglitazone versus other thiazolidinediones | Preclinical | Melanoma cell lines | Effects on cycle arrest, p21, cyclin D1, pRB hypophosphorylation are better than with other thiazolidinediones |
|
