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Review

Pregnane X Receptor, Constitutive Androstane Receptor and Hepatocyte Nuclear Factors as Emerging Players in Cancer Precision Medicine

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Pages 1547-1571 | Received 27 May 2016, Accepted 07 Jul 2016, Published online: 26 Aug 2016

References

  • De Mattia E , CecchinE , ToffoliG . Pharmacogenomics of intrinsic and acquired pharmacoresistance in colorectal cancer: toward targeted personalized therapy . Drug Resist. Updat.20 , 39 – 70 ( 2015 ).
  • Caudle KE , ThornCF , KleinTEet al. Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing . Clin. Pharmacol. Ther.94 ( 6 ), 640 – 645 ( 2013 ).
  • Swen JJ , NijenhuisM , de BoerAet al. Pharmacogenetics: from bench to byte-an update of guidelines . Clin. Pharmacol. Ther.89 ( 5 ), 662 – 673 ( 2011 ).
  • PharmaGKB . www.pharmagkb.org .
  • Chen S , VilleneuveL , JonkerDet al. ABCC5 and ABCG1 polymorphisms predict irinotecan-induced severe toxicity in metastatic colorectal cancer patients . Pharmacogenet. Genomics25 ( 12 ), 573 – 583 ( 2015 ).
  • Chen S , LaverdiereI , TourancheauAet al. A novel UGT1 marker associated with better tolerance against irinotecan-induced severe neutropenia in metastatic colorectal cancer patients . Pharmacogenomics J.15 ( 6 ), 513 – 520 ( 2015 ).
  • De Mattia E , ToffoliG , PoleselJet al. Pharmacogenetics of ABC and SLC transporters in metastatic colorectal cancer patients receiving first-line FOLFIRI treatment . Pharmacogenet. Genomics23 ( 10 ), 549 – 557 ( 2013 ).
  • De Re V , CannizzaroR , CanzonieriVet al. MTHFR polymorphisms in gastric cancer and in first-degree relatives of patients with gastric cancer . Tumour Biol.31 ( 1 ), 23 – 32 ( 2010 ).
  • Kalia M . Biomarkers for personalized oncology: recent advances and future challenges . Metabolism64 ( 3 Suppl. 1 ), S16 – S21 ( 2015 ).
  • Levesque E , BelangerAS , HarveyMet al. Refining the UGT1A haplotype associated with irinotecan-induced hematological toxicity in metastatic colorectal cancer patients treated with 5-fluorouracil/irinotecan-based regimens . J. Pharmacol. Exp. Ther.345 ( 1 ), 95 – 101 ( 2013 ).
  • Toffoli G , GiodiniL , BuonadonnaAet al. Clinical validity of a DPYD-based pharmacogenetic test to predict severe toxicity to fluoropyrimidines . Int. J Cancer137 ( 12 ), 2971 – 2980 ( 2015 ).
  • Cecchin E , De MattiaE , ToffoliG . Nuclear receptors and drug metabolism for the personalization of cancer therapy . Expert Opin. Drug Metab. Toxicol.12 ( 3 ), 291 – 306 ( 2016 ).
  • De Mattia E , DreussiE , CecchinE , ToffoliG . Pharmacogenetics of the nuclear hormone receptors: the missing link between environment and drug effects?Pharmacogenomics14 ( 16 ), 2035 – 2054 ( 2013 ).
  • Chai X , ZengS , XieW . Nuclear receptors PXR and CAR: implications for drug metabolism regulation, pharmacogenomics and beyond . Expert Opin. Drug Metab. Toxicol.9 ( 3 ), 253 – 266 ( 2013 ).
  • Mukherjee S , ManiS . Orphan nuclear receptors as targets for drug development . Pharm. Res.27 ( 8 ), 1439 – 1468 ( 2010 ).
  • Mangelsdorf DJ , ThummelC , BeatoMet al. The nuclear receptor superfamily: the second decade . Cell83 ( 6 ), 835 – 839 ( 1995 ).
  • Chen Y , TangY , GuoC , WangJ , BoralD , NieD . Nuclear receptors in the multidrug resistance through the regulation of drug-metabolizing enzymes and drug transporters . Biochem. Pharmacol.83 ( 8 ), 1112 – 1126 ( 2012 ).
  • Azmi AS , BaoGW , GaoJ , MohammadRM , SarkarFH . Network insights into the genes regulated by hepatocyte nuclear factor 4 in response to drug induced perturbations: a review . Curr. Drug Discov. Technol.10 ( 2 ), 147 – 154 ( 2013 ).
  • Hwang-Verslues WW , SladekFM . HNF4alpha-role in drug metabolism and potential drug target?Curr. Opin. Pharmacol.10 ( 6 ), 698 – 705 ( 2010 ).
  • Kobayashi K , HashimotoM , HonkakoskiP , NegishiM . Regulation of gene expression by CAR: an update . Arch. Toxicol.89 ( 7 ), 1045 – 1055 ( 2015 ).
  • Pondugula SR , ManiS . Pregnane xenobiotic receptor in cancer pathogenesis and therapeutic response . Cancer Lett.328 ( 1 ), 1 – 9 ( 2013 ).
  • Wallace BD , RedinboMR . Xenobiotic-sensing nuclear receptors involved in drug metabolism: a structural perspective . Drug Metab Rev.45 ( 1 ), 79 – 100 ( 2013 ).
  • Gonzalez FJ . Regulation of hepatocyte nuclear factor 4 alpha-mediated transcription . Drug Metab. Pharmacokinet.23 ( 1 ), 2 – 7 ( 2008 ).
  • Banerjee M , RobbinsD , ChenT . Targeting xenobiotic receptors PXR and CAR in human diseases . Drug Discov. Today20 ( 5 ), 618 – 628 ( 2015 ).
  • Cressman AM , PetrovicV , Piquette-MillerM . Inflammation-mediated changes in drug transporter expression/activity: implications for therapeutic drug response . Expert Rev. Clin. Pharmacol.5 ( 1 ), 69 – 89 ( 2012 ).
  • Crusz SM , BalkwillFR . Inflammation and cancer: advances and new agents . Nat. Rev. Clin. Oncol.12 ( 10 ), 584 – 596 ( 2015 ).
  • Grivennikov SI , GretenFR , KarinM . Immunity, inflammation, and cancer . Cell140 ( 6 ), 883 – 899 ( 2010 ).
  • Harvey RD , MorganET . Cancer, inflammation, and therapy: effects on cytochrome p450-mediated drug metabolism and implications for novel immunotherapeutic agents . Clin. Pharmacol. Ther.96 ( 4 ), 449 – 457 ( 2014 ).
  • Petrovic V , TengS , Piquette-MillerM . Regulation of drug transporters during infection and inflammation . Mol. Interv.7 ( 2 ), 99 – 111 ( 2007 ).
  • Ghose R , MallickP , TanejaG , ChuC , MoorthyB . In vitro approaches to study regulation of hepatic cytochrome P450 (CYP) 3A expression by paclitaxel and rifampicin . Methods Mol. Biol.1395 , 55 – 68 ( 2016 ).
  • Chellappa K , RobertsonGR , SladekFM . HNF4alpha: a new biomarker in colon cancer?Biomark. Med.6 ( 3 ), 297 – 300 ( 2012 ).
  • Shim JH , LeeHC , HanS , KangHJ , YuE , LeeSG . Hepatocyte nuclear factor 1beta is a novel prognostic marker independent of the Milan criteria in transplantable hepatocellular carcinoma: a retrospective analysis based on tissue microarrays . Liver Transpl.19 ( 3 ), 336 – 345 ( 2013 ).
  • Shim JH , KangHJ , HanSet al. Prognostic value of hepatocyte nuclear factors 4alpha and 1alpha identified by tissue microarray in resectable hepatocellular carcinoma . J. Gastroenterol. Hepatol.29 ( 3 ), 524 – 532 ( 2014 ).
  • Walesky C , ApteU . Role of hepatocyte nuclear factor 4alpha (HNF4alpha) in cell proliferation and cancer . Gene Expr.16 ( 3 ), 101 – 108 ( 2015 ).
  • Yuan RH , LaiHS , HsuHC , LaiPL , JengYM . Expression of bile duct transcription factor HNF1beta predicts early tumor recurrence and is a stage-independent prognostic factor in hepatocellular carcinoma . J. Gastrointest. Surg.18 ( 10 ), 1784 – 1794 ( 2014 ).
  • Robbins D , ChenT . Tissue-specific regulation of pregnane X receptor in cancer development and therapy . Cell Biosci.4 ( 1 ), 17 ( 2014 ).
  • Raynal C , PascussiJM , LeguelinelGet al. Pregnane X receptor (PXR) expression in colorectal cancer cells restricts irinotecan chemosensitivity through enhanced SN-38 glucuronidation . Mol. Cancer9 , 46 ( 2010 ).
  • Basseville A , PreisserL , de CarnéTrécessonSet al. Irinotecan induces steroid and xenobiotic receptor (SXR) signaling to detoxification pathway in colon cancer cells . Mol. Cancer10 , 80 ( 2011 ).
  • Harmsen S , MeijermanI , FebusCL , Maas-BakkerRF , BeijnenJH , SchellensJH . PXR-mediated induction of P-glycoprotein by anticancer drugs in a human colon adenocarcinoma-derived cell line . Cancer Chemother. Pharmacol.66 ( 4 ), 765 – 771 ( 2010 ).
  • Jiang H , ChenK , HeJet al. Association of pregnane X receptor with multidrug resistance-related protein 3 and its role in human colon cancer chemoresistance . J. Gastrointest. Surg.13 ( 10 ), 1831 – 1838 ( 2009 ).
  • Harmsen S , MeijermanI , Maas-BakkerRF , BeijnenJH , SchellensJH . PXR-mediated P-glycoprotein induction by small molecule tyrosine kinase inhibitors . Eur. J. Pharm. Sci.48 ( 4–5 ), 644 – 649 ( 2013 ).
  • Milczarek M , Filip-PsurskaB , SwietnickiW , KutnerA , WietrzykJ . Vitamin D analogs combined with 5-fluorouracil in human HT-29 colon cancer treatment . Oncol. Rep.32 ( 2 ), 491 – 504 ( 2014 ).
  • Xu F , WangF , YangT , ShengY , ZhongT , ChenY . Differential drug resistance acquisition to doxorubicin and paclitaxel in breast cancer cells . Cancer Cell Int.14 ( 1 ), 538 ( 2014 ).
  • Qiao EQ , YangHJ . Effect of pregnane X receptor expression on drug resistance in breast cancer . Oncol. Lett.7 ( 4 ), 1191 – 1196 ( 2014 ).
  • Chen Y , TangY , ChenS , NieD . Regulation of drug resistance by human pregnane X receptor in breast cancer . Cancer Biol. Ther.8 ( 13 ), 1265 – 1272 ( 2009 ).
  • Choi HK , YangJW , RohSH , HanCY , KangKW . Induction of multidrug resistance associated protein 2 in tamoxifen-resistant breast cancer cells . Endocr. Relat. Cancer14 ( 2 ), 293 – 303 ( 2007 ).
  • Masuyama H , NakatsukasaH , TakamotoN , HiramatsuY . Down-regulation of pregnane X receptor contributes to cell growth inhibition and apoptosis by anticancer agents in endometrial cancer cells . Mol. Pharmacol.72 ( 4 ), 1045 – 1053 ( 2007 ).
  • Takami N , SakamotoH , YamamotoT . Steroid and xenobiotic receptor (SXR) is a key system for the acquisition of cisplatin resistance in endometrial cancer cells . J. Int. Med. Res.31 ( 2 ), 59 – 68 ( 2003 ).
  • Gupta D , VenkateshM , WangHet al. Expanding the roles for pregnane X receptor in cancer: proliferation and drug resistance in ovarian cancer . Clin. Cancer Res.14 ( 17 ), 5332 – 5340 ( 2008 ).
  • Shigetomi H , SudoT , ShimadaKet al. Inhibition of cell death and induction of G2 arrest accumulation in human ovarian clear cells by HNF-1beta transcription factor: chemosensitivity is regulated by checkpoint kinase CHK1 . Int. J Gynecol. Cancer24 ( 5 ), 838 – 843 ( 2014 ).
  • Amano Y , MandaiM , YamaguchiKet al. Metabolic alterations caused by HNF1beta expression in ovarian clear cell carcinoma contribute to cell survival . Oncotarget6 ( 28 ), 26002 – 26017 ( 2015 ).
  • Lopes-Coelho F , Gouveia-FernandesS , GoncalvesLGet al. HNF1beta drives glutathione (GSH) synthesis underlying intrinsic carboplatin resistance of ovarian clear cell carcinoma (OCCC) . Tumour Biol.37 ( 4 ), 4813 – 4829 ( 2016 ).
  • Chen Y , TangY , WangMT , ZengS , NieD . Human pregnane X receptor and resistance to chemotherapy in prostate cancer . Cancer Res.67 ( 21 ), 10361 – 10367 ( 2007 ).
  • Kumar S , JaiswalB , KumarS , NegiS , TyagiRK . Cross-talk between androgen receptor and pregnane and xenobiotic receptor reveals existence of a novel modulatory action of anti-androgenic drugs . Biochem. Pharmacol.80 ( 7 ), 964 – 976 ( 2010 ).
  • Wang T , MaX , KrauszKW , IdleJR , GonzalezFJ . Role of pregnane X receptor in control of all-trans retinoic acid (ATRA) metabolism and its potential contribution to ATRA resistance . J. Pharmacol. Exp. Ther.324 ( 2 ), 674 – 684 ( 2008 ).
  • Wang D , LiL , YangHet al. The constitutive androstane receptor is a novel therapeutic target facilitating cyclophosphamide-based treatment of hematopoietic malignancies . Blood121 ( 2 ), 329 – 338 ( 2013 ).
  • Hedrich WD , XiaoJ , HeywardSet al. Activation of the constitutive androstane receptor increases the therapeutic index of CHOP in lymphoma treatment . Mol. Cancer Ther.15 ( 3 ), 392 – 401 ( 2016 ).
  • Mensah-Osman EJ , ThomasDG , TabbMMet al. Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines . Cancer109 ( 5 ), 957 – 965 ( 2007 ).
  • Rigalli JP , ReuterT , Herold-MendeCet al. Minor role of pregnane-X-receptor for acquired multidrug resistance in head and neck squamous cell carcinoma in vitro . Cancer Chemother. Pharmacol.71 ( 5 ), 1335 – 1343 ( 2013 ).
  • MacLeod AK , McLaughlinLA , HendersonCJ , WolfCR . Activation status of the pregnane X receptor influences vemurafenib availability in humanized mouse models . Cancer Res.75 ( 21 ), 4573 – 4581 ( 2015 ).
  • Rigalli JP , CiriaciN , AriasAet al. Regulation of multidrug resistance proteins by genistein in a hepatocarcinoma cell line: impact on sorafenib cytotoxicity . PLoS ONE10 ( 3 ), e0119502 ( 2015 ).
  • Fukumasu H , RochettiAL , PiresPRet al. Constitutive androstane receptor ligands modulate the anti-tumor efficacy of paclitaxel in non-small cell lung cancer cells . PLoS ONE9 ( 6 ), e99484 ( 2014 ).
  • Hagos Y , WegnerW , KuehneAet al. HNF4alpha induced chemosensitivity to oxaliplatin and 5-FU mediated by OCT1 and CNT3 in renal cell carcinoma . J. Pharm. Sci.103 ( 10 ), 3326 – 3334 ( 2014 ).
  • Ansari D , UreyC , HilmerssonKSet al. Apicidin sensitizes pancreatic cancer cells to gemcitabine by epigenetically regulating MUC4 expression . Anticancer Res.34 ( 10 ), 5269 – 5276 ( 2014 ).
  • Noll EM , EisenC , StenzingerAet al. CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma . Nat. Med.22 ( 3 ), 278 – 287 ( 2016 ).
  • Hassen W , KassambaraA , RemeTet al. Drug metabolism and clearance system in tumor cells of patients with multiple myeloma . Oncotarget6 ( 8 ), 6431 – 6447 ( 2015 ).
  • Kong Q , HanZ , ZuoX , WeiH , HuangW . Co-expression of pregnane X receptor and ATP-binding cassette sub-family B member 1 in peripheral blood: a prospective indicator for drug resistance prediction in non-small cell lung cancer . Oncol. Lett.11 ( 5 ), 3033 – 3039 ( 2016 ).
  • Yamaguchi H , HishinumaT , EndoNet al. Genetic variation in ABCB1 influences paclitaxel pharmacokinetics in Japanese patients with ovarian cancer . Int. J. Gynecol. Cancer16 ( 3 ), 979 – 985 ( 2006 ).
  • Lim HS , JuLH , SeokLK , SookLE , JangIJ , RoJ . Clinical implications of CYP2D6 genotypes predictive of tamoxifen pharmacokinetics in metastatic breast cancer . J. Clin. Oncol.25 ( 25 ), 3837 – 3845 ( 2007 ).
  • Tham LS , HolfordNH , HorSYet al. Lack of association of single-nucleotide polymorphisms in pregnane X receptor, hepatic nuclear factor 4alpha, and constitutive androstane receptor with docetaxel pharmacokinetics . Clin. Cancer Res.13 ( 23 ), 7126 – 7132 ( 2007 ).
  • Kiyotani K , MushirodaT , KuboM , ZembutsuH , SugiyamaY , NakamuraY . Association of genetic polymorphisms in SLCO1B3 and ABCC2 with docetaxel-induced leukopenia . Cancer Sci.99 ( 5 ), 967 – 972 ( 2008 ).
  • Hor SY , LeeSC , WongCIet al. PXR, CAR and HNF4alpha genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients . Pharmacogenomics J.8 ( 2 ), 139 – 146 ( 2008 ).
  • Sandanaraj E , LalS , SelvarajanVet al. PXR pharmacogenetics: association of haplotypes with hepatic CYP3A4 and ABCB1 messenger RNA expression and doxorubicin clearance in Asian breast cancer patients . Clin. Cancer Res.14 ( 21 ), 7116 – 7126 ( 2008 ).
  • Gandara DR , KawaguchiT , CrowleyJet al. Japanese–US common-arm analysis of paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a model for assessing population-related Pharmacogenomics . J. Clin Oncol27 ( 21 ), 3540 – 3546 ( 2009 ).
  • van Erp NP , EechouteK , van der VeldtAAet al. Pharmacogenetic pathway analysis for determination of sunitinib-induced toxicity . J. Clin. Oncol.27 ( 26 ), 4406 – 4412 ( 2009 ).
  • van der Veldt AA , EechouteK , GelderblomHet al. Genetic polymorphisms associated with a prolonged progression-free survival in patients with metastatic renal cell cancer treated with sunitinib . Clin. Cancer Res.17 ( 3 ), 620 – 629 ( 2011 ).
  • Xu CF , BingNX , BallHAet al. Pazopanib efficacy in renal cell carcinoma: evidence for predictive genetic markers in angiogenesis-related and exposure-related genes . J. Clin. Oncol.29 ( 18 ), 2557 – 2564 ( 2011 ).
  • Singh O , ChanJY , LinK , HengCC , ChowbayB . SLC22A1–ABCB1 haplotype profiles predict imatinib pharmacokinetics in Asian patients with chronic myeloid leukemia . PLoS ONE7 ( 12 ), e51771 ( 2012 ).
  • Beuselinck B , KaradimouA , LambrechtsDet al. Single-nucleotide polymorphisms associated with outcome in metastatic renal cell carcinoma treated with sunitinib . Br. J. Cancer108 ( 4 ), 887 – 900 ( 2013 ).
  • Tang NL , LiaoCD , WangXet al. Role of pharmacogenetics on adjuvant chemotherapy-induced neutropenia in Chinese breast cancer patients . J. Cancer Res. Clin. Oncol.139 ( 3 ), 419 – 427 ( 2013 ).
  • Chew SC , LimJ , SinghOet al. Pharmacogenetic effects of regulatory nuclear receptors (PXR, CAR, RXRalpha and HNF4alpha) on docetaxel disposition in Chinese nasopharyngeal cancer patients . Eur. J. Clin. Pharmacol.70 ( 2 ), 155 – 166 ( 2014 ).
  • Diekstra MH , LiuX , SwenJJet al. Association of single nucleotide polymorphisms in IL8 and IL13 with sunitinib-induced toxicity in patients with metastatic renal cell carcinoma . Eur. J. Clin. Pharmacol.71 ( 12 ), 1477 – 1484 ( 2015 ).
  • Mbatchi LC , SchmittA , ThomasFet al. Polymorphisms in SLCO1B3 and NR1I2 as genetic determinants of hematotoxicity of carboplatin and paclitaxel combination . Pharmacogenomics16 ( 13 ), 1439 – 1450 ( 2015 ).
  • Narjoz C , CessotA , Thomas-SchoemannAet al. Role of the lean body mass and of pharmacogenetic variants on the pharmacokinetics and pharmacodynamics of sunitinib in cancer patients . Invest. New Drugs33 ( 1 ), 257 – 268 ( 2015 ).
  • Mbatchi LC , RobertJ , YchouMet al. Effect of single nucleotide polymorphisms in the xenobiotic-sensing receptors NR1I2 and NR1I3 on the pharmacokinetics and toxicity of irinotecan in colorectal cancer patients . Clin. Pharmacokinet. ( 2016 ) ( Epub ahead of print ).
  • Mandato VD , FarnettiE , TorricelliFet al. HNF1B polymorphism influences the prognosis of endometrial cancer patients: a cohort study . BMC Cancer15 , 229 ( 2015 ).
  • Fujita K , KubotaY , IshidaH , SasakiY . Irinotecan, a key chemotherapeutic drug for metastatic colorectal cancer . World J. Gastroenterol.21 ( 43 ), 12234 – 12248 ( 2015 ).
  • Cecchin E , RussoA , CoronaGet al. UGT1A1*28 polymorphism in ovarian cancer patients . Oncol. Rep.12 ( 2 ), 457 – 462 ( 2004 ).
  • Cecchin E , RussoA , CampagnuttaE , MartellaL , ToffoliG . Lack of association of CYP1B1*3 polymorphism and ovarian cancer in a Caucasian population . Int. J. Biol. Markers19 ( 2 ), 160 – 163 ( 2004 ).
  • Lamba J , LambaV , StromS , VenkataramananR , SchuetzE . Novel single nucleotide polymorphisms in the promoter and intron 1 of human pregnane X receptor/NR1I2 and their association with CYP3A4 expression . Drug Metab. Dispos.36 ( 1 ), 169 – 181 ( 2008 ).
  • Libra M , NavolanicPM , TalaminiRet al. Thymidylate synthetase mRNA levels are increased in liver metastases of colorectal cancer patients resistant to fluoropyrimidine-based chemotherapy . BMC. Cancer4 , 11 ( 2004 ).
  • Anglesio MS , CareyMS , KobelM , MackayH , HuntsmanDG . Clear cell carcinoma of the ovary: a report from the first Ovarian Clear Cell Symposium, June 24th, 2010 . Gynecol. Oncol.121 ( 2 ), 407 – 415 ( 2011 ).
  • Sugiyama T , KamuraT , KigawaJet al. Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy . Cancer88 ( 11 ), 2584 – 2589 ( 2000 ).
  • Kozyra M , Ingelman-SundbergM , LauschkeVM . Rare genetic variants in cellular transporters, metabolic enzymes, and nuclear receptors can be important determinants of interindividual differences in drug response . Genet. Med. doi:10.1038/gim.2016.33 ( 2016 ) ( Epub ahead of print ).
  • Lauschke VM , Ingelman-SundbergM . Precision medicine and rare genetic variants . Trends Pharmacol. Sci.37 ( 2 ), 85 – 86 ( 2016 ).
  • Dreussi E , BiasonP , ToffoliG , CecchinE . miRNA pharmacogenomics: the new frontier for personalized medicine in cancer?Pharmacogenomics13 ( 14 ), 1635 – 1650 ( 2012 ).
  • Dreussi E , PucciarelliS , PaoliAet al. Predictive role of microRNA-related genetic polymorphisms in the pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients . Oncotarget doi:10.18632/oncotarget.7757 ( 2016 ) ( Epub ahead of print ).
  • Ingelman-Sundberg M , CascorbiI . Pharmacogenomic or -epigenomic biomarkers in drug treatment: two sides of the same medal?Clin. Pharmacol. Ther.99 ( 5 ), 478 – 480 ( 2016 ).
  • Cherian MT , LinW , WuJ , ChenT . CINPA1 is an inhibitor of constitutive androstane receptor that does not activate pregnane X receptor . Mol. Pharmacol.87 ( 5 ), 878 – 889 ( 2015 ).
  • Lin W , YangL , ChaiSC , LuY , ChenT . Development of CINPA1 analogs as novel and potent inverse agonists of constitutive androstane receptor . Eur. J Med. Chem.108 , 505 – 528 ( 2016 ).

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