[1] SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2020. CA Cancer J Clin, 2020, 70(1):7-30.
[2] FORNER A, REIG M, BRUIX J. Hepatocellular carcinoma. Lancet, 2018, 391(10127):1301-1314.
[3] VILLANUEVA A. Hepatocellular carcinoma. N Engl J Med, 2019, 380(15):1450-1462.
[4] CHOI K J, BAIK I H, YE S K, et al. Molecular targeted therapy for hepatocellular carcinoma: present status and future directions. Biol Pharm Bull, 2015, 38(7):986-991.
[5] YAMAMOTO S, KONDO S. Oral chemotherapy for the treatment of hepatocellular carcinoma. Expert Opin Pharmacother, 2018, 19(9):993-1001.
[6] CUCCHETTI A, PISCAGLIA F, PINNA A D, et al. Efficacy and safety of systemic therapies for advanced hepatocellular carcinoma: an network Meta-analysis of phase Ⅲ trials. Liver Cancer, 2017, 6(4):337-348.
[7] BRUIX J, QIN S, MERLE P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE):a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 2017, 389(10064):56-66.
[8] VERMA H, SINGH BAHIA M, CHOUDHARY S, et al. Drug metabolizing enzymes-associated chemo resistance and strategies to overcome it. Drug Metab Rev, 2019, 51(2):196-223.
[9] TRUNZER K, PAVLICK A C, SCHUCHTER L, et al. Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma. J Clin Oncol, 2013, 31(14):1767-1774.
[10] HOLOHAN C, VAN SCHAEYBROECK S, LONGLEY D B, et al. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer, 2013, 13(10):714-726.
[11] JOVE M, SPENCER J, CLENCH M, et al. Precision pharmacology: mass spectrometry imaging and pharmacokinetic drug resistance. Crit Rev Oncol Hematol, 2019, 141:153-162.
[12] ROBEY R W, PLUCHINO K M, HALL M D, et al. Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat Rev Cancer, 2018, 18(7):452-464.
[13] WANG R, ZHANG T, YANG Z, et al. Long non-coding RNA FTH1P3 activates paclitaxel resistance in breast cancer through miR-206/ABCB1. J Cell Mol Med, 2018, 22(9):4068-4075.
[14] WU D D, LI X S, MENG X N, et al. MicroRNA-873 mediates multidrug resistance in ovarian cancer cells by targeting ABCB1. Tumour Biol, 2016, 37(8):10499-10506.
[15] ZHAO Y, QI X, CHEN J, et al. The miR-491-3p/Sp3/ABCB1 axis attenuates multidrug resistance of hepatocellular carcinoma. Cancer Lett, 2017, 408:102-111.
[16] SU Z, LIU G, FANG T, et al. Silencing MRP1-4 genes by RNA interference enhances sensitivity of human hepatoma cells to chemotherapy. Am J Transl Res, 2016, 8(6):2790-2802.
[17] LI W, ZHANG H, ASSARAF Y G, et al. Overcoming ABC transporter-mediated multidrug resistance: molecular mechanisms and novel therapeutic drug strategies. Drug Resist Updat, 2016, 27:14-29.
[18] CEBALLOS M P, RIGALLI J P, CERÉ L I, et al. ABC transporters: regulation and association with multidrug resistance in hepatocellular carcinoma and colorectal carcinoma. Curr Med Chem, 2019, 26(7):1224-1250.
[19] DONG J, QIN Z, ZHANG W D, et al. Medicinal chemistry strategies to discover P-glycoprotein inhibitors: an update. Drug Resist Updat, 2020, 49:100681
[20] BOREL F, HAN R, VISSER A, et al. Adenosine triphosphate-binding cassette transporter genes up-regulation in untreated hepatocellular carcinoma is mediated by cellular microRNAs. Hepatology (Baltimore, Md.), 2012, 55(3):821-832.
[21] COLOMBO F, TROMBETTA E, CETRANGOLO P, et al. Giant lysosomes as a chemotherapy resistance mechanism in hepatocellular carcinoma cells. PLoS One, 2014, 9(12):e114787-e114787.
[22] RIGALLI J P, CIRIACI N, ARIAS A, et al. Regulation of multidrug resistance proteins by genistein in a hepatocarcinoma cell line: impact on sorafenib cytotoxicity. PLoS One, 2015, 10(3):e0119502-e0119502.
[23] LIANG Y, ZHENG T, SONG R, et al. Hypoxia-mediated sorafenib resistance can be overcome by EF24 through Von Hippel-Lindau tumor suppressor-dependent HIF-1α inhibition in hepatocellular carcinoma. Hepatology (Baltimore, Md.), 2013, 57(5):1847-1857.
[24] JETTER A, KULLAK-UBLICK G A. Drugs and hepatic transporters: a review. Pharmacol Res, 2020,154:104234.
[25] KEPPLER D. Multidrug resistance proteins (MRPs, ABCCs):importance for pathophysiology and drug therapy. Handb Exp Pharmacol, 2011,(201):299-323.
[26] JOHNSON Z L, CHEN J. Structural basis of substrate recognition by the multidrug resistance protein MRP1. Cell, 2017, 168(6):1075-1085.
[27] FOUQUET G, DEBUYSSCHER V, OULED-HADDOU H, et al. Hepatocyte SLAMF3 reduced specifically the multidrugs resistance protein MRP-1 and increases HCC cells sensitization to anti-cancer drugs. Oncotarget, 2016, 7(22):32493-32503.
[28] KATAOKA J, SHIRAHA H, HORIGUCHI S, et al. Loss of runt-related transcription factor 3 induces resistance to 5-fluorouracil and cisplatin in hepatocellular carcinoma. Oncol Rep, 2016, 35(5):2576-2582.
[29] LING S, LI J, SHAN Q, et al. USP22 mediates the multidrug resistance of hepatocellular carcinoma via the SIRT1/AKT/MRP1 signaling pathway. Mol Oncol, 2017, 11(6):682-695.
[30] LIN S, HOFFMANN K, XIAO Z, et al. MEK inhibition induced downregulation of MRP1 and MRP3 expression in experimental hepatocellular carcinoma. Cancer Cell Int, 2013, 13(1):3-3.
[31] COLE S P C. Targeting multidrug resistance protein 1 (MRP1, ABCC1):past, present, and future. Annu Rev Pharmacol Toxicol, 2014, 54:95-117.
[32] TANDIA M, MHIRI A, PAULE B, et al. Correlation between clinical response to sorafenib in hepatocellular carcinoma treatment and polymorphisms of P-glycoprotein (ABCB1) and of breast cancer resistance protein (ABCG2):monocentric study. Cancer Chemother Pharmacol, 2017, 79(4):759-766.
[33] CHEN Y L, CHEN P M, LIN P Y, et al. ABCG2 overexpression confers poor outcomes in hepatocellular carcinoma of elderly patients. Anticancer Res, 2016, 36(6):2983-2988.
[34] SUKOWATI C H, ROSSO N, PASCUT D, et al. Gene and functional up-regulation of the BCRP/ABCG2 transporter in hepatocellular carcinoma. BMC Gastroenterol, 2012, 12:160.
[35] SUN Z, ZHAO Z, LI G, et al. Relevance of two genes in the multidrug resistance of hepatocellular carcinoma: in vivo and clinical studies. Tumori, 2010, 96(1):90-96.
[36] KONG J, QIU Y, LI Y, et al. TGF-β1 elevates P-gp and BCRP in hepatocellular carcinoma through HOTAIR/miR-145 axis. Biopharm Drug Dispos, 2019, 40(2):70-80.
[37] BHAGYARAJ E, AHUJA N, KUMAR S, et al. TGF-β induced chemoresistance in liver cancer is modulated by xenobiotic nuclear receptor PXR. Cell Cycle, 2019, 18(24):3589-3602.
[38] LI H, ZHOU S, LI T, et al. Suppression of BCRP expression and restoration of sensitivity to chemotherapy in multidrug-resistant HCC cell line HEPG2/ADM by RNA interference. Hepatogastroenterology, 2012, 59(119):2238-2242.
[39] TAKAHASHI K, YAN I K, WOOD J, et al. Involvement of extracellular vesicle long noncoding RNA (linc-VLDLR) in tumor cell responses to chemotherapy. Mol Cancer Res, 2014, 12(10):1377-1387.
[40] SOUSA D, LIMA R T, VASCONCELOS M H. Intercellular transfer of cancer drug resistance traits by extracellular vesicles. Trends Mol Med, 2015, 21(10):595-608.
[41] YANG X R, XU Y, YU B, et al. High expression levels of putative hepatic stem/progenitor cell biomarkers related to tumour angiogenesis and poor prognosis of hepatocellular carcinoma. Gut, 2010, 59(7):953-962.
[42] SHI G M, XU Y, FAN J, et al. Identification of side population cells in human hepatocellular carcinoma cell lines with stepwise metastatic potentials. J Cancer Res Clin Oncol, 2008, 134(11):1155-1163.
[43] FUNG S W, CHEUNG P F, YIP C W, et al. The ATP-binding cassette transporter ABCF1 is a hepatic oncofetal protein that promotes chemoresistance, EMT and cancer stemness in hepatocellular carcinoma. Cancer Lett, 2019, 457:98-109.
[44] NAMISAKI T, SCHAEFFELER E, FUKUI H, et al. Differential expression of drug uptake and efflux transporters in Japanese patients with hepatocellular carcinoma. Drug Metab Dispos, 2014, 42(12):2033-2040.
[45] ROBEY R W, PLUCHINO K M, HALL M D, et al. Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat Rev Cancer, 2018, 18(7):452-464.
[46] LI R, XU T, WANG H, et al. Dysregulation of the miR-325-3p/DPAGT1 axis supports HBV-positive HCC chemoresistance. Biochem Biophys Res Commun, 2019, 519(2):358-365.
[47] KIMCHI-SARFATY C, OH J M, KIM I W, et al. A "silent" polymorphism in the MDR1 gene changes substrate specificity. Science, 2007, 315(5811):525-528.
[48] SU Z, LIU G, FANG T, et al. Silencing MRP1-4 genes by RNA interference enhances sensitivity of human hepatoma cells to chemotherapy. Am J Transl Res, 2016, 8(6):2790-2802.
[49] ZHAO J, YU B Y, WANG D Y, et al. Promoter polymorphism of MRP1 associated with reduced survival in hepatocellular carcinoma. World J Gastroenterol, 2010, 16(48):6104-6110.
[50] TANDIA M, MHIRI A, PAULE B, et al. Correlation between clinical response to sorafenib in hepatocellular carcinoma treatment and polymorphisms of P-glycoprotein (ABCB1) and of breast cancer resistance protein (ABCG2):monocentric study. Cancer Chemother Pharmacol, 2017, 79(4):759-766.
[51] DI GIACOMO S, BRIZ O, MONTE M J, et al. Chemosensitization of hepatocellular carcinoma cells to sorafenib by β-caryophyllene oxide-induced inhibition of ABC export pumps. Arch Toxicol, 2019, 93(3):623-634.
[52] FENG S, LI A, ZHENG Y C, et al. Role of drug-metabolizing enzymes in cancer and cancer therapy. Curr Drug Metab, 2020, 21(1):67-76.
[53] UNDERHILL G H, KHETANI S R. Advances in engineered human liver platforms for drug metabolism studies. Drug Metab Dispos, 2018, 46(11):1626-1637.
[54] LI Y, STEPPI A, ZHOU Y, et al. Tumoral expression of drug and xenobiotic metabolizing enzymes in breast cancer patients of different ethnicities with implications to personalized medicine. Sci Rep, 2017, 7(1):4747-4747.
[55] KULMA I, BOONPRASERT K, NA-BANGCHANG K. Polymorphisms of genes encoding drug transporters or cytochrome P450 enzymes and association with clinical response in cancer patients: a systematic review. Cancer Chemother Pharmacol, 2019, 84(5):959-975.
[56] GUO X G, WANG Z H, DONG W, et al. Specific CYP450 genotypes in the Chinese population affect sorafenib toxicity in HBV/HCV-associated hepatocellular carcinoma patients. Biomed Environ Sci, 2018, 31(8):586-595.
[57] UL-ISLAM S, AHMED M B, SHEHZAD A, et al. Failure of chemotherapy in hepatocellular carcinoma due to impaired and dysregulated primary liver drug metabolizing enzymes and drug transport proteins: what to do?. Curr Drug Metab, 2018, 19(10):819-829.
[58] CHEN C H, FERREIRA J C B, GROSS E R, et al. Targeting aldehyde dehydrogenase 2: new therapeutic opportunities. Physiol Rev, 2014, 94(1):1-34.
[59] AHMED LASKAR A, YOUNUS H. Aldehyde toxicity and metabolism: the role of aldehyde dehydrogenases in detoxification, drug resistance and carcinogenesis. Drug Metab Rev, 2019, 51(1):42-64.
[60] TOMITA H, TANAKA K, TANAKA T, et al. Aldehyde dehydrogenase 1A1 in stem cells and cancer. Oncotarget, 2016, 7(10):11018-11032.
[61] CALDERARO J, NAULT J C, BIOULAC-SAGE P, et al. ALDH3A1 is overexpressed in a subset of hepatocellular carcinoma characterised by activation of the Wnt/β-catenin pathway. Virchows Arch, 2014, 464(1):53-60.
[62] LAI S C, SU Y T, CHI C C, et al. DNMT3b/OCT4 expression confers sorafenib resistance and poor prognosis of hepatocellular carcinoma through IL-6/STAT3 regulation. J Exp Clin Cancer Res, 2019, 38(1):474-474.
[63] WILSON G S, HU Z, DUAN W, et al. Efficacy of using cancer stem cell markers in isolating and characterizing liver cancer stem cells. Stem Cells Dev, 2013, 22(19):2655-2664.
[64] NIO K, YAMASHITA T, KANEKO S. The evolving concept of liver cancer stem cells. Molecular Cancer, 2017, 16(1):4.
[65] CASTELLI G, PELOSI E, TESTA U. Liver cancer: molecular characterization, clonal evolution and cancer stem cells. Cancers (Basel), 2017, 9(9):127.
[66] TOLEDO-GUZMÁN M E, HERNÁNDEZ M I, GÓMEZ-GALLEGOSÁ A, et al. ALDH as a stem cell marker in solid tumors. Curr Stem Cell Res Ther, 2019, 14(5):375-388.
[67] YAN T, GAO S, PENG X, et al. Significantly decreased and more variable expression of major CYPs and UGTs in liver microsomes prepared from HBV-positive human hepatocellular carcinoma and matched pericarcinomatous tissues determined using an isotope label-free UPLC-MS/MS method. Pharm Res, 2015, 32(3):1141-1157.
[68] LU L, ZHOU J, SHI J, et al. Drug-metabolizing activity, protein and gene expression of UDP-glucuronosyltransferases are significantly altered in hepatocellular carcinoma patients. PLoS One, 2015, 10(5):e0127524-e0127524.
[69] BRANDON E F A, SPARIDANS R W, MEIJERMAN I, et al. In vitro characterization of the biotransformation of thiocoraline, a novel marine anti-cancer drug. Invest New Drugs, 2004, 22(3):241-251.
[70] EVANCHIK M J, ALLEN D, YOBURN J C, et al. Metabolism of (+)-1,4-dihydro-7-(trans-3-methoxy-4-methylamino-1-pyrrolidinyl)-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid (voreloxin, formerly SNS-595), a novel replication-dependent DNA-damaging agent. Drug Metab Dispos, 2009, 37(3):594-601.
[71] GE Y, CHEN S, MU W, et al. Epigenetic regulation of UDP-glucuronosyltransferase by microRNA-200a/-183: implications for responses to sorafenib treatment in patients with hepatocellular carcinoma. Cancer Lett, 2019, 454:14-25.
[72] GOLDSTEIN I, RIVLIN N, SHOSHANA O Y, et al. Chemotherapeutic agents induce the expression and activity of their clearing enzyme CYP3A4 by activating p53. Carcinogenesis, 2013, 34(1):190-198.
[73] MEECH R, HU D G, MCKINNON R A, et al. The UDP-glycosyltransferase (UGT) superfamily: new members, new functions, and novel paradigms. Physiol Rev, 2019, 99(2):1153-1222.
[74] MAZERSKA Z, MRÓZ A, PAWŁOWSKA M, et al. The role of glucuronidation in drug resistance. Pharmacol Ther, 2016, 159:35-55.
[75] HU D G, MACKENZIE P I, MCKINNON R A, et al. Genetic polymorphisms of human UDP-glucuronosyltransferase (UGT) genes and cancer risk. Drug Metab Rev, 2016, 48(1):47-69.
[76] YAN T, LU L, XIE C, et al. Severely impaired and dysregulated cytochrome P450 expression and activities in hepatocellular carcinoma: implications for personalized treatment in patients. Mol Cancer Ther, 2015, 14(12):2874-2886.
[77] ZHOU J, WEN Q, LI S F, et al. Significant change of cytochrome P450s activities in patients with hepatocellular carcinoma. Oncotarget, 2016, 7(31):50612-50623.
[78] KAMDEM L K, FLOCKHART D A, DESTA Z, In vitro cytochrome P450-mediated metabolism of exemestane. Drug Metab Dispos, 2011, 39(1):98-105.
[79] CHEN H, SHEN Z Y, XU W, et al. Expression of P450 and nuclear receptors in normal and end-stage Chinese livers. World J Gastroenterol, 2014, 20(26):8681-8690.
[80] TIBBS Z E, ROHN-GLOWACKI K J, CRITTENDEN F, et al. Structural plasticity in the human cytosolic sulfotransferase dimer and its role in substrate selectivity and catalysis. Drug Metab Pharmacokinet, 2015, 30(1):3-20.
[81] WANG X R, QU Z Q, LI X D, et al. Activity of sulfotransferase 1A1 is dramatically upregulated in patients with hepatocellular carcinoma secondary to chronic hepatitis B virus infection. Cancer Sci, 2010, 101(2):412-415.
[82] ZHOU H, LI Y, SONG X, et al. CHST11/13 regulate the metastasis and chemosensitivity of human hepatocellular carcinoma cells via mitogen-activated protein kinase pathway. Dig Dis Sci, 2016, 61(7):1972-1985.
[83] PLJESA-ERCEGOVAC M, SAVIC-RADOJEVIC A, MATIC M, et al. Glutathione transferases: potential targets to overcome chemoresistance in solid tumors. Int J Mol Sci, 2018, 19(12):3785.
[84] MISHRA M, JAYAL P, KARANDE A A, et al. Identification of a co-target for enhancing efficacy of sorafenib in HCC through a quantitative modeling approach. FEBS J, 2018, 285(21):3977-3992.
[85] WEI L, LEE D, LAW C T, et al. Genome-wide CRISPR/Cas9 library screening identified PHGDH as a critical driver for Sorafenib resistance in HCC. Nat Commun, 2019, 10(1):4681.
[86] ZHU W P, LIU Z Y, ZHAO Y M, et al. Dihydropyrimidine dehydrogenase predicts survival and response to interferon-α in hepatocellular carcinoma. Cell Death Dis, 2018, 9(2):69.
[87] OKANO Y, KURAMOCHI H, NAKAJIMA G, et al. Elevated levels of mRNAs encoding dihydropyrimidine dehydrogenase and thymidylate synthase are associated with improved survival of patients with hepatocellular carcinoma treated with S-1. Oncol Lett, 2017, 14(1):930-936.
[88] WANG C, FANG P F, CAI H L. Research progress of ABC membrane transporters and their regulation in tumor drug resistance and new mechanism of detoxification. Chin Pharm J(中国药学杂志), 2017, 52(22):1961-1965.
[89] ZHENG J Q, WANG Q, YANG X, et al. Research progress in toxic effects of antitumor drugs mediated by drug metabolism enzymes and isoforms. Chin Pharm J(中国药学杂志), 2017, 52(13):1115-1119.