Nuclear receptors and pathogenesis of pancreatic cancer

Table 2 Expression of nuclear receptors and clinical trials

Nuclear receptor	Expression in primary PDAC	Clinical trials and results
PPAR (-α, -β, -γ)	PPARα: Unknown	None for PPARa and β/δ;
	PPARβ/δ: overexpressed; expression correlates with tumor stage, recurrence, and distant metastasis	PPARγ: TZD apparently reduce the risk of PDAC but PPARγ agonists do not improve survival
	PPARg: maybe overexpressed; expression correlates with shorter overall survival
RAR and RXR (-α, -β, -γ)	Yes (with the exception of RARb that is apparently lost during cancer development)	13-cis-RA in combination with IFN-γ: prolonged stable disease as well no improvement have been reported
AR	Yes	Phase II trials with the antagonist flutamide: increase in survival as well no effect have been reported
ER (-α, -β)	Yes	Tamoxifen with no benefit
NR4A1, NR4A2, NR4A3	NR4A1: overexpressed	None
	NR4A2 and NR4A3: unknown
LHR-1	Overexpressed	None
COUP-TFII	Overexpressed; expression correlates with shorter overall survival, tumor stage, and presence of metastasis	None

PPAR: Peroxisome proliferator-activated receptor; PDAC: Pancreatic ductal carcinoma; TZD: Thiazolidinediones; IFN: Interferon; RAR: Retinoic acid receptor; RXR: Retinoid X receptor; AR: Androgen receptor; ER: Estrogen receptor; LHR-1: Liver receptor homologue-1 receptor; COUP-TFII: Chicken ovalbumin upstream promoter transcription factor II.