Table 1: Clinical trials and some preclinical studies for evaluation of PPARs and their ligands in cancer development and anticancer therapy.

ReferencesNuclear receptorTreatmentClinical phaseNumber of patientsHuman tumors or cell typesMain conclusions of the authors

Demetri et al., 1999 [148]PPARγTroglitazone (per os, 1 × 800 mg/d, 6 weeks)Phase II3High-grade liposarcomasInduction of cell differentiation in a human solid tumors
Debrock et al., 2003 [149]PPARγrosiglitazone (4 mg/d for 1 year)Phase II12LiposarcomaIncreased PPARγ activity: no correlation with clinical outcome

Prostate cancer
Mueller et al., 2000 [150]PPARγTroglitazone (per os, 2 × 400 mg/d, 12 weeks)Phase II41Human prostate cancerProlonged 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 development193 (versus 188 controls)Prostate cancerNo association of prostate cancer and Pro12Ala polymorphism
Xu et al., 2003 [152]PPARγTosiglitazonePreclinicalPrimary culture of human prostatic cancer cellsProdifferentiating properties of thiazolidinediones
Dawson and Slovin, 2003 [153]Vit D PPARγReviewProstate cancers
Smith et al., 2004 [154]PPARγRosiglitazone 2 × 4 mg/d 338 d (versus placebo 315 d)Phase II105Prostate carcinoma without recent hormone therapy and with a rise in PSA after radical prostatectomy and/or radiation without metastasisNo advantage over placebo efficacy and PPARγ do not contribute to prostate cancer development
Saif et al., 2009 [155]PPARγ agonist and LTB4 receptor antagonistLY29311 (in combination with gemcitabine)Phase II67 (combined therapy) versus 66 (gemcitabine alone)Advanced pancreatic carcinomaNo benefit obtained by adding LY293111 to gemcitabine

Colo-rectal cancer
Kulke et al., 2002 [156]PPARγTroglitazone per osPhase II25Chemoresistant colorectal metastatic cancerNo objective tumor response
Choi et al., 2008 [157]PPARγ15d-PGJ2 pioglitazonePreclinicalAPC-mutated HT-29 human colon cancer cellsPPARγ ligand promotes growth of APC-muted HT-29 colon cancer cells
Dai and Wang, 2010 [158]PPARγReviewColorectal cancerMechanisms by which PPARγ impacts carcinogenesis in colorectal cancer
Tenenbaum et al., 2008 [159]All PPARsPanagonist bezafibrate retard 400 mg/dBezafibrate Infarctus Prevention (BIP) study3011 with coronary artery disease and no cancer1506 given bezafibrate 1505 given placeboExperimental support for preventive effects of bezafibrate towards colon cancer
Breast cancer
Burstein et al., 2003 [160]PPARγTroglitazone 800 mg/d for 6 monthsPhase II22Breast cancer refractory to one chemotherapy or two hormonal therapiesLittle 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]PPARγ1RNAiPreclinicalMCF-7 breast cancer cellsPPARγ1 signaling impacts balance between proliferation and apoptosis towards proliferation in breast cancer

Hasegawa et al., 2007 [163]PPARγFuligocondis B via increase in PGJ2PreclinicalLeukemia cells15d-PGJ2 sensitizes TRAIL-resistant cells to TRAIL independent on PPARγ
Tsao et al., 2010 [164]PPARγ2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) 15d-PGJ2Preclinical Phase I9Acute myelogenous leukemia cell lines from 9 patientsPPARγ regulates apoptosis via activation of caspase 8 and co-activator DRIP205 promotes cell differentiation by PPARγ

Thyroid cancer
Kebebew et al., 2006 [165]PPARγRosiglitazone 4 mg/d 1 week + 8 mg/d 7 weeksPhase II10 patientsDifferentiated thyroid cancerRosiglitazone may induce radioiodine uptake in some patients possibly via PPARγ-independent pathways
Tepmongkol et al., 2008 [166]PPARγRosiglitazone 8 mg/d for 6 weeksPhase II23Thyroid carcinomaIncrease of radioiodine uptake in thyroid tumors possibly via PPARγ-independent mechanisms

Glioma and glioblastoma, lung cancer
Yao et al., 2006 [167]HMG-CoA reductase PPARγLovastatin + troglitazonePreclinicalGlioblastoma and lung cancer cell linesInduction of P27 [Kip 1] (statines), E2F-1 (glitazone), + CDK2, cyclin A. Rb phosphorylation status
Hau et al., 2008 [168]COX-2 inhibitors PPARγRofecoxib pioglitazole in association with low-dose chemotherapyPhase II44High-grade gliomas (glioblastomas or anaplastic glioma)Moderate activity encouraging future utilization in highly selected patients

Head and neck cancer
Schweitzer et al., 2010 [169]PPARγReviewHead and neck cancersTherapeutic use of PPARγ ligands in head and neck cancer

Botton et al., 2009 [170]PPARγCiglitazone versus other thiazolidinedionesPreclinicalMelanoma cell linesEffects on cycle arrest, p21, cyclin D1, pRB hypophosphorylation are better than with other thiazolidinediones