Potential Treatment Strategies for Hepatocellular Carcinoma Cell Sensitization to Sorafenib

References

• Zhu AX, Kang Y-K, Yen C-J, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, Phase 3 trial. Lancet Oncol. 2019;20(2):282–296. doi:10.1016/S1470-2045(18)30937-9
   PubMed Web of Science ®Google Scholar
• Nishida N, Kitano M, Sakurai T, Kudo M. Molecular mechanism and prediction of sorafenib chemoresistance in human hepatocellular carcinoma. Dig Dis. 2015;33(6):771–779. doi:10.1159/000439102
   PubMed Web of Science ®Google Scholar
• Sonbol MB, Riaz IB, Naqvi SAA, et al. Systemic therapy and sequencing options in advanced hepatocellular carcinoma. JAMA Oncol. 2020;6(12):e204930. doi:10.1001/jamaoncol.2020.4930
   PubMed Web of Science ®Google Scholar
• Wu L-W, Zhou D-M, Zhang Z-Y, et al. Suppression of LSD1 enhances the cytotoxic and apoptotic effects of regorafenib in hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2019;512(4):852–858. doi:10.1016/j.bbrc.2019.03.154
   PubMed Web of Science ®Google Scholar
• Li Y-L, Zhang N-Y, Hu X, et al. Evodiamine induces apoptosis and promotes hepatocellular carcinoma cell death induced by vorinostat via downregulating HIF-1α under hypoxia. Biochem Biophys Res Commun. 2018;498(3):481–486. doi:10.1016/j.bbrc.2018.03.004
   PubMed Web of Science ®Google Scholar
• Bao MH-R, Wong CC-L. Hypoxia, metabolic reprogramming, and drug resistance in liver cancer. Cells. 2021;10(7):1715. doi:10.3390/cells10071715
   PubMed Web of Science ®Google Scholar
• Chowdhury R, Hardy A, Schofield CJ. The human oxygen sensing machinery and its manipulation. Chem Soc Rev. 2008;37(7):1308. doi:10.1039/b701676j
   PubMed Web of Science ®Google Scholar
• Maxwell PH, Wiesener MS, Chang G-W, et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature. 1999;399(6733):271–275. doi:10.1038/20459
   PubMed Web of Science ®Google Scholar
• Méndez-Blanco C, Fondevila F, García-Palomo A, González-Gallego J, Mauriz JL. Sorafenib resistance in hepatocarcinoma: role of hypoxia-inducible factors. Exp Mol Med. 2018;50(10):1–9. doi:10.1038/s12276-018-0159-1
   PubMed Web of Science ®Google Scholar
• Mu H, Yu G, Li H, et al. Mild chronic hypoxia-induced HIF-2α interacts with c-MYC through competition with HIF-1α to induce hepatocellular carcinoma cell proliferation. Cell Oncol. 2021;44(5):1151–1166. doi:10.1007/s13402-021-00625-w
   Web of Science ®Google Scholar
• Chen JC-H, Chuang H-Y, Liao Y-J, et al. Enhanced cytotoxicity of human hepatocellular carcinoma cells following pretreatment with sorafenib combined with trichostatin A. Oncol Lett. 2019;17(1):638–645. doi:10.3892/ol.2018.9582
   PubMed Web of Science ®Google Scholar
• Liu L-P, Ho RLK, Chen GG, Lai PBS. Sorafenib inhibits hypoxia-inducible factor-1α synthesis: implications for antiangiogenic activity in hepatocellular carcinoma. Clin Cancer Res. 2012;18(20):5662–5671. doi:10.1158/1078-0432.CCR-12-0552
   PubMed Web of Science ®Google Scholar
• 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. 2013;57(5):1847–1857. doi:10.1002/hep.26224
   PubMed Web of Science ®Google Scholar
• Tredan O, Galmarini CM, Patel K, Tannock IF. Drug resistance and the solid tumor microenvironment. J Natl Cancer Inst. 2007;99(19):1441–1454. doi:10.1093/jnci/djm135
   PubMed Web of Science ®Google Scholar
• Bahman AA, Abaza MSI, Khoushiash SI, Al-Attiyah RJ. Sequence‑dependent effect of sorafenib in combination with natural phenolic compounds on hepatic cancer cells and the possible mechanism of action. Int J Mol Med. 2018;42(3):1695–1715. doi:10.3892/ijmm.2018.3725
   PubMed Web of Science ®Google Scholar
• Wu F-Q, Fang T, Yu L-X, et al. ADRB2 signaling promotes HCC progression and sorafenib resistance by inhibiting autophagic degradation of HIF1α. J Hepatol. 2016;65(2):314–324. doi:10.1016/j.jhep.2016.04.019
   PubMed Web of Science ®Google Scholar
• Xie L, Xiao K, Whalen EJ, et al. Oxygen-regulated β 2 -adrenergic receptor hydroxylation by EGLN3 and ubiquitylation by pVHL. Sci Signal. 2009;2(78):ra33–ra33. doi:10.1126/scisignal.2000444
   PubMed Web of Science ®Google Scholar
• Liu X, Zhang X, Peng Z, et al. Deubiquitylase OTUD6B governs pVHL stability in an Enzyme-independent manner and suppresses hepatocellular carcinoma metastasis. Adv Sci. 2020;7(8):1902040. doi:10.1002/advs.201902040
   Web of Science ®Google Scholar
• Feng J, Dai W, Mao Y, et al. Simvastatin re-sensitizes hepatocellular carcinoma cells to sorafenib by inhibiting HIF-1α/PPAR-γ/PKM2-mediated glycolysis. J Exp Clin Cancer Res. 2020;39(1):24. doi:10.1186/s13046-020-1528-x
   PubMed Web of Science ®Google Scholar
• Albadari N, Deng S, Li W. The transcriptional factors HIF-1 and HIF-2 and their novel inhibitors in cancer therapy. Expert Opin Drug Discov. 2019;14(7):667–682. doi:10.1080/17460441.2019.1613370
   PubMed Web of Science ®Google Scholar
• Gonzalez FJ, Xie C, Jiang C. The role of hypoxia-inducible factors in metabolic diseases. Nat Rev Endocrinol. 2019;15(1):21–32. doi:10.1038/s41574-018-0096-z
   Web of Science ®Google Scholar
• Wilson GK, Tennant DA, McKeating JA. Hypoxia inducible factors in liver disease and hepatocellular carcinoma: current understanding and future directions. J Hepatol. 2014;61(6):1397–1406. doi:10.1016/j.jhep.2014.08.025
   PubMed Web of Science ®Google Scholar
• Ma L, Li G, Zhu H, et al. 2-Methoxyestradiol synergizes with sorafenib to suppress hepatocellular carcinoma by simultaneously dysregulating hypoxia-inducible factor-1 and −2. Cancer Lett. 2014;355(1):96–105. doi:10.1016/j.canlet.2014.09.011
   PubMed Web of Science ®Google Scholar
• Dong X-F, Liu T-Q, Zhi X-T, et al. COX-2/PGE2 axis regulates HIF2α activity to promote hepatocellular carcinoma hypoxic response and reduce the sensitivity of sorafenib treatment. Clin Cancer Res. 2018;24(13):3204–3216. doi:10.1158/1078-0432.CCR-17-2725
   PubMed Web of Science ®Google Scholar
• Fu Q-H, Zhang Q, Zhang J-Y, et al. LB-100 sensitizes hepatocellular carcinoma cells to the effects of sorafenib during hypoxia by activation of Smad3 phosphorylation. Tumour Biol. 2016;37(6):7277–7286. doi:10.1007/s13277-015-4560-2
   PubMedGoogle Scholar
• You A, Cao M, Guo Z, et al. Metformin sensitizes sorafenib to inhibit postoperative recurrence and metastasis of hepatocellular carcinoma in orthotopic mouse models. J Hematol Oncol. 2016;9:20. doi:10.1186/s13045-016-0253-6
   PubMed Web of Science ®Google Scholar
• Ling S, Song L, Fan N, et al. Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway. Int J Oncol. 2017;50(1):297–309. doi:10.3892/ijo.2016.3799
   PubMed Web of Science ®Google Scholar
• Yang Q, Guo X, Yang L. Metformin enhances the effect of regorafenib and inhibits recurrence and metastasis of hepatic carcinoma after liver resection via regulating expression of hypoxia inducible factors 2α (HIF-2α) and 30 kDa HIV Tat-Interacting Protein (TIP30). Med Sci Monit. 2018;24:2225–2234. doi:10.12659/msm.906687
   PubMed Web of Science ®Google Scholar
• Lo J, Lau EY, Ching RH, et al. Nuclear factor kappa B-mediated CD47 up-regulation promotes sorafenib resistance and its blockade synergizes the effect of sorafenib in hepatocellular carcinoma in mice. Hepatology. 2015;62(2):534–545. doi:10.1002/hep.27859
   PubMed Web of Science ®Google Scholar
• Cheng BY, Lau EY, Leung H-W, et al. IRAK1 augments cancer stemness and drug resistance via the AP-1/AKR1B10 signaling cascade in hepatocellular carcinoma. Cancer Res. 2018;78(9):2332–2342. doi:10.1158/0008-5472.CAN-17-2445
   PubMed Web of Science ®Google Scholar
• Alsaied OA, Sangwan V, Banerjee S, et al. Sorafenib and triptolide as combination therapy for hepatocellular carcinoma. Surgery. 2014;156(2):270–279. doi:10.1016/j.surg.2014.04.055
   PubMed Web of Science ®Google Scholar
• Ma L, Liu W, Xu A, et al. Activator of thyroid and retinoid receptor increases sorafenib resistance in hepatocellular carcinoma by facilitating the Warburg effect. Cancer Sci. 2020;111(6):2028–2040. doi:10.1111/cas.14412
   PubMed Web of Science ®Google Scholar
• Yuan H, Li A-J, Ma S-L, et al. Inhibition of autophagy significantly enhances combination therapy with sorafenib and HDAC inhibitors for human hepatoma cells. World J Gastroenterol. 2014;20(17):4953–4962. doi:10.3748/wjg.v20.i17.4953
   PubMed Web of Science ®Google Scholar
• Hsu F-T, Liu Y-C, Chiang IT, et al. Sorafenib increases efficacy of vorinostat against human hepatocellular carcinoma through transduction inhibition of vorinostat-induced ERK/NF-κB signaling. Int J Oncol. 2014;45(1):177–188. doi:10.3892/ijo.2014.2423
   PubMed Web of Science ®Google Scholar
• Hamed HA, Yamaguchi Y, Fisher PB, Grant S, Dent P. Sorafenib and HDAC inhibitors synergize with TRAIL to kill tumor cells. J Cell Physiol. 2013;228(10):1996–2005. doi:10.1002/jcp.24362
   PubMed Web of Science ®Google Scholar
• Tak WY, Ryoo B-Y, Lim HY, et al. Phase I/II study of first-line combination therapy with sorafenib plus resminostat, an oral HDAC inhibitor, versus sorafenib monotherapy for advanced hepatocellular carcinoma in east Asian patients. Invest New Drugs. 2018;36(6):1072–1084. doi:10.1007/s10637-018-0658-x
   PubMed Web of Science ®Google Scholar
• Raoul J-L, Forner A, Bolondi L, Cheung TT, Kloeckner R, de Baere T. Updated use of TACE for hepatocellular carcinoma treatment: how and when to use it based on clinical evidence. Cancer Treat Rev. 2019;72:28–36. doi:10.1016/j.ctrv.2018.11.002
   PubMed Web of Science ®Google Scholar
• Omyła-Staszewska J, Deptała A. Effective therapeutic management of hepatocellular carcinoma – on the basis of a clinical case [Polish version: skuteczne postępowanie terapeutyczne w nieresekcyjnym raku wątrobowokomórkowym – na przykładzie przypadku klinicznego p. 64]. Contemp Oncol. 2012;1:60–67. doi:10.5114/wo.2012.27339
   Google Scholar
• Kudo M, Ueshima K, Ikeda M, et al. Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial. Gut. 2020;69(8):1492–1501. doi:10.1136/gutjnl-2019-318934
   PubMed Web of Science ®Google Scholar
• Zhang T, Huang W, Dong H, Chen Y. Trans-catheter arterial chemoembolization plus Sorafenib, an unsuccessful therapy in the treatment of hepatocellular carcinoma? Medicine. 2020;99(29):e20962. doi:10.1097/MD.0000000000020962
   PubMed Web of Science ®Google Scholar
• Li Z. Cell apoptosis and regeneration of hepatocellular carcinoma after transarterial chemoembolization. WJG. 2004;10(13):1876. doi:10.3748/wjg.v10.i13.1876
   PubMed Web of Science ®Google Scholar
• Faubert B, Solmonson A, DeBerardinis RJ. Metabolic reprogramming and cancer progression. Science. 2020;368:6487. doi:10.1126/science.aaw5473
   Web of Science ®Google Scholar
• Reinfeld BI, Madden MZ, Wolf MM, et al. Cell-programmed nutrient partitioning in the tumour microenvironment. Nature. 2021. doi:10.1038/s41586-021-03442-1
   PubMed Web of Science ®Google Scholar
• Kim M-J, Choi Y-K, Park SY, et al. PPARδ reprograms glutamine metabolism in sorafenib-resistant HCC. Mol Cancer Res. 2017;15(9):1230–1242. doi:10.1158/1541-7786.MCR-17-0061
   PubMed Web of Science ®Google Scholar
• Dai W, Xu L, Yu X, et al. OGDHL silencing promotes hepatocellular carcinoma by reprogramming glutamine metabolism. J Hepatol. 2020;72(5):909–923. doi:10.1016/j.jhep.2019.12.015
   PubMed Web of Science ®Google Scholar
• Lally JSV, Ghoshal S, DePeralta DK, et al. Inhibition of Acetyl-CoA carboxylase by phosphorylation or the inhibitor ND-654 suppresses lipogenesis and hepatocellular carcinoma. Cell Metab. 2019;29(1):174–182.e5. doi:10.1016/j.cmet.2018.08.020
   PubMed Web of Science ®Google Scholar
• Xu IM-J, Lai RK-H, Lin S-H, et al. Transketolase counteracts oxidative stress to drive cancer development. Proc Natl Acad Sci U S A. 2016;113(6):E725–E734. doi:10.1073/pnas.1508779113
   PubMed Web of Science ®Google Scholar
• Lee D, Xu IM-J, Chiu DK-C, et al. Folate cycle enzyme MTHFD1L confers metabolic advantages in hepatocellular carcinoma. J Clin Invest. 2017;127(5):1856–1872. doi:10.1172/JCI90253
   PubMed Web of Science ®Google Scholar
• Zhou K, Liu Y, Luger K. Histone chaperone FACT facilitates chromatin transcription: mechanistic and structural insights. Curr Opin Struct Biol. 2020;65:26–32. doi:10.1016/j.sbi.2020.05.019
   PubMed Web of Science ®Google Scholar
• Shen J, Chen M, Lee D, et al. Histone chaperone FACT complex mediates oxidative stress response to promote liver cancer progression. Gut. 2020;69(2):329–342. doi:10.1136/gutjnl-2019-318668
   PubMed Web of Science ®Google Scholar
• Tuo L, Xiang J, Pan X, et al. PCK1 downregulation promotes TXNRD1 expression and hepatoma cell growth via the Nrf2/Keap1 pathway. Front Oncol. 2018;8:611. doi:10.3389/fonc.2018.00611
   PubMed Web of Science ®Google Scholar
• Lee D, Xu IM-J, Chiu DK-C, et al. Induction of oxidative stress through inhibition of thioredoxin reductase 1 is an effective therapeutic approach for hepatocellular carcinoma. Hepatology. 2019;69(4):1768–1786. doi:10.1002/hep.30467
   PubMed Web of Science ®Google Scholar
• Sacco R, Leuci D, Tortorella C, et al. Transforming growth factor beta1 and soluble Fas serum levels in hepatocellular carcinoma. Cytokine. 2000;12(6):811–814.
   PubMed Web of Science ®Google Scholar
• Lin T-H, Shao -Y-Y, Chan S-Y, Huang C-Y, Hsu C-H, Cheng A-L. High serum transforming growth factor-β1 levels predict outcome in hepatocellular carcinoma patients treated with sorafenib. Clin Cancer Res. 2015;21(16):3678–3684. doi:10.1158/1078-0432.CCR-14-1954
   PubMed Web of Science ®Google Scholar
• Matsuda Y, Wakai T, Kubota M, et al. Valproic acid overcomes transforming growth factor-β-mediated sorafenib resistance in hepatocellular carcinoma. Int J Clin Exp Pathol. 2014;7(4):1299–1313.
   PubMed Web of Science ®Google Scholar
• Liu J, Yang X, Liang Q, Yu Y, Shen X, Sun G. Valproic acid overcomes sorafenib resistance by reducing the migration of Jagged2-mediated Notch1 signaling pathway in hepatocellular carcinoma cells. Int J Biochem Cell Biol. 2020;126:105820. doi:10.1016/j.biocel.2020.105820
   PubMed Web of Science ®Google Scholar
• Ungerleider N, Han C, Zhang J, Yao L, Wu T. TGFβ signaling confers sorafenib resistance via induction of multiple RTKs in hepatocellular carcinoma cells. Mol Carcinog. 2017;56(4):1302–1311. doi:10.1002/mc.22592
   PubMed Web of Science ®Google Scholar
• Xu Y, Huang J, Ma L, et al. MicroRNA-122 confers sorafenib resistance to hepatocellular carcinoma cells by targeting IGF-1R to regulate RAS/RAF/ERK signaling pathways. Cancer Lett. 2016;371(2):171–181. doi:10.1016/j.canlet.2015.11.034
   PubMed Web of Science ®Google Scholar
• Ezzoukhry Z, Louandre C, Trécherel E, et al. EGFR activation is a potential determinant of primary resistance of hepatocellular carcinoma cells to sorafenib. Int J Cancer. 2012;131(12):2961–2969. doi:10.1002/ijc.27604
   PubMed Web of Science ®Google Scholar
• Lin C-Y, Gustafsson J-Å. Targeting liver X receptors in cancer therapeutics. Nat Rev Cancer. 2015;15(4):216–224. doi:10.1038/nrc3912
   PubMed Web of Science ®Google Scholar
• Shao W, Zhu W, Lin J, et al. Liver X receptor agonism sensitizes a subset of hepatocellular carcinoma to sorafenib by dual-inhibiting MET and EGFR. Neoplasia. 2020;22(1):1–9. doi:10.1016/j.neo.2019.08.002
   PubMed Web of Science ®Google Scholar
• Xia S, Pan Y, Liang Y, Xu J, Cai X. The microenvironmental and metabolic aspects of sorafenib resistance in hepatocellular carcinoma. EBioMedicine. 2020;51. doi:10.1016/j.ebiom.2019.102610
   Web of Science ®Google Scholar
• Tai W-T, Shiau C-W, Chen P-J, et al. Discovery of novel Src homology region 2 domain-containing phosphatase 1 agonists from sorafenib for the treatment of hepatocellular carcinoma. Hepatology. 2014;59(1):190–201. doi:10.1002/hep.26640
   PubMed Web of Science ®Google Scholar
• Long J, Jiang C, Liu B, et al. Maintenance of stemness by miR-589-5p in hepatocellular carcinoma cells promotes chemoresistance via STAT3 signaling. Cancer Lett. 2018;423:113–126. doi:10.1016/j.canlet.2017.11.031
   PubMed Web of Science ®Google Scholar
• Wang J, Zhou M, Jin X, et al. Glycochenodeoxycholate induces cell survival and chemoresistance via phosphorylation of STAT3 at Ser727 site in HCC. J Cell Physiol. 2020;235(3):2557–2568. doi:10.1002/jcp.29159
   PubMed Web of Science ®Google Scholar
• Duan Z, Foster R, Bell DA, et al. Signal transducers and activators of transcription 3 pathway activation in drug-resistant ovarian cancer. Clin Cancer Res. 2006;12(17):5055–5063.
   PubMed Web of Science ®Google Scholar
• Ji T, Gong D, Han Z, et al. Abrogation of constitutive Stat3 activity circumvents cisplatin resistant ovarian cancer. Cancer Lett. 2013;341(2):231–239. doi:10.1016/j.canlet.2013.08.022
   PubMed Web of Science ®Google Scholar
• Hung M-H, Tai W-T, Shiau C-W, Chen K-F. Downregulation of signal transducer and activator of transcription 3 by sorafenib: a novel mechanism for hepatocellular carcinoma therapy. World J Gastroenterol. 2014;20(41):15269–15274. doi:10.3748/wjg.v20.i41.15269
   PubMed Web of Science ®Google Scholar
• Blechacz BRA, Smoot RL, Bronk SF, Werneburg NW, Sirica AE, Gores GJ. Sorafenib inhibits signal transducer and activator of transcription-3 signaling in cholangiocarcinoma cells by activating the phosphatase shatterproof 2. Hepatology. 2009;50(6):1861–1870. doi:10.1002/hep.23214
   PubMed Web of Science ®Google Scholar
• Tai W-T, Cheng A-L, Shiau C-W, et al. Dovitinib induces apoptosis and overcomes sorafenib resistance in hepatocellular carcinoma through SHP-1-mediated inhibition of STAT3. Mol Cancer Ther. 2012;11(2):452–463. doi:10.1158/1535-7163.MCT-11-0412
   PubMed Web of Science ®Google Scholar
• Su J-C, Tseng P-H, Wu S-H, et al. SC-2001 overcomes STAT3-mediated sorafenib resistance through RFX-1/SHP-1 activation in hepatocellular carcinoma. Neoplasia. 2014;16(7):595–605. doi:10.1016/j.neo.2014.06.005
   PubMed Web of Science ®Google Scholar
• Leung CON, Tong M, Chung KPS, et al. Overriding adaptive resistance to sorafenib through combination therapy with src homology 2 domain-containing phosphatase 2 blockade in hepatocellular carcinoma. Hepatology. 2020;72(1):155–168. doi:10.1002/hep.30989
   PubMed Web of Science ®Google Scholar
• Han P, Li H, Jiang X, et al. Dual inhibition of Akt and c-Met as a second-line therapy following acquired resistance to sorafenib in hepatocellular carcinoma cells. Mol Oncol. 2017;11(3):320–334. doi:10.1002/1878-0261.12039
   PubMed Web of Science ®Google Scholar
• Tovar V, Cornella H, Moeini A, et al. Tumour initiating cells and IGF/FGF signalling contribute to sorafenib resistance in hepatocellular carcinoma. Gut. 2017;66(3):530–540. doi:10.1136/gutjnl-2015-309501
   PubMed Web of Science ®Google Scholar
• Wang F, Bank T, Malnassy G, et al. Inhibition of insulin-like growth factor 1 receptor enhances the efficacy of sorafenib in inhibiting hepatocellular carcinoma cell growth and survival. Hepatol Commun. 2018;2(6):732–746. doi:10.1002/hep4.1181
   PubMed Web of Science ®Google Scholar
• Singh AR, Joshi S, Burgoyne AM, et al. Single agent and synergistic activity of the “First-in-Class” dual PI3K/BRD4 Inhibitor SF1126 with sorafenib in hepatocellular carcinoma. Mol Cancer Ther. 2016;15(11):2553–2562. doi:10.1158/1535-7163.MCT-15-0976
   PubMed Web of Science ®Google Scholar
• Abdelmoneem MA, Elnaggar MA, Hammady RS, et al. Dual-targeted lactoferrin shell-oily core nanocapsules for synergistic targeted/herbal therapy of hepatocellular carcinoma. ACS Appl Mater Interfaces. 2019;11(30):26731–26744. doi:10.1021/acsami.9b10164
   PubMed Web of Science ®Google Scholar
• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA a Cancer J Clin. 2020;70(1):7–30. doi:10.3322/caac.21590
   PubMed Web of Science ®Google Scholar
• Fu R, Jiang S, Li J, Chen H, Zhang X. Activation of the HGF/c-MET axis promotes lenvatinib resistance in hepatocellular carcinoma cells with high c-MET expression. Med Oncol. 2020;37(4). doi:10.1007/s12032-020-01350-4
   PubMed Web of Science ®Google Scholar
• 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). doi:10.1038/s41467-019-12606-7
   Google Scholar