Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.
Article
PubMed
Google Scholar
Cheng A-L, Kang Y-K, Chen Z, Tsao C-J, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25–34.
Article
CAS
PubMed
Google Scholar
Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim T-Y, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894–905.
Article
CAS
PubMed
Google Scholar
Bruix J, Qin S, Merle P, Granito A, Huang Y-H, Bodoky G, 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.
Article
CAS
PubMed
Google Scholar
Kudo M, Finn RS, Qin S, Han K-H, Ikeda K, Piscaglia F, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163–73.
Article
CAS
PubMed
Google Scholar
Abou-Alfa GK, Meyer T, Cheng AL, El-Khoueiry AB, Rimassa L, Ryoo BY, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379(1):54–63.
Article
CAS
PubMed
PubMed Central
Google Scholar
Zhu AX, Kang Y-K, Yen C-J, Finn RS, Galle PR, Llovet JM, 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):282–96.
Article
CAS
PubMed
Google Scholar
Vogel A, Cervantes A, Chau I, Daniele B, Llovet JM, Meyer T, et al. Hepatocellular carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29:iv238–iv55.
Article
CAS
PubMed
Google Scholar
Vogel A, Martinelli E. Updated treatment recommendations for hepatocellular carcinoma (HCC) from the ESMO clinical practice guidelines. Ann Oncol. 2021;32(6):801–5.
Article
CAS
PubMed
Google Scholar
Manasanch EE, Orlowski RZ. Proteasome inhibitors in cancer therapy. Nat Rev Clin Oncol. 2017;14(7):417–33.
Article
CAS
PubMed
PubMed Central
Google Scholar
Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352(24):2487–98.
Article
CAS
PubMed
Google Scholar
Fisher RI, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, et al. Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2006;24(30):4867–74.
Article
PubMed
Google Scholar
Goy A, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, et al. Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study. Ann Oncol. 2009;20(3):520–5.
Article
CAS
PubMed
Google Scholar
Niewerth D, Jansen G, Assaraf YG, Zweegman S, Kaspers GJL, Cloos J. Molecular basis of resistance to proteasome inhibitors in hematological malignancies. Drug Resist Updat. 2015;18:18–35.
Article
PubMed
Google Scholar
Corso A, Mangiacavalli S, Varettoni M, Pascutto C, Zappasodi P, Lazzarino M. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comparison between previously treated and untreated patients. Leuk Res. 2010;34(4):471–4.
Article
CAS
PubMed
Google Scholar
Arastu-Kapur S, Anderl JL, Kraus M, Parlati F, Shenk KD, Lee SJ, et al. Nonproteasomal targets of the proteasome inhibitors bortezomib and carfilzomib: a link to clinical adverse events. Clin Cancer Res. 2011;17(9):2734–43.
Article
CAS
PubMed
Google Scholar
Lonial S, Waller EK, Richardson PG, Jagannath S, Orlowski RZ, Giver CR, et al. Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma. Blood. 2005;106(12):3777–84.
Article
CAS
PubMed
PubMed Central
Google Scholar
Herndon TM, Deisseroth A, Kaminskas E, Kane RC, Koti KM, Rothmann MD, et al. U.S. Food and Drug Administration approval: carfilzomib for the treatment of multiple myeloma. Clin Cancer Res. 2013;19(17):4559.
Article
CAS
PubMed
Google Scholar
Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Špička I, Oriol A, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2014;372(2):142–52.
Article
PubMed
CAS
Google Scholar
Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374(17):1621–34.
Article
CAS
PubMed
Google Scholar
Roeten MSF, Cloos J, Jansen G. Positioning of proteasome inhibitors in therapy of solid malignancies. Cancer Chemother Pharmacol. 2018;81(2):227–43.
Article
CAS
PubMed
Google Scholar
Aghajanian C, Soignet S, Dizon DS, Pien CS, Adams J, Elliott PJ, et al. A phase I trial of the novel proteasome inhibitor PS341 in advanced solid tumor malignancies. Clin Cancer Res. 2002;8(8):2505–11.
CAS
PubMed
Google Scholar
Kim GP, Mahoney MR, Szydlo D, Mok TSK, Marshke R, Holen K, et al. An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma. Investig New Drugs. 2012;30(1):387–94.
Article
CAS
Google Scholar
Huang IT, Dhungel B, Shrestha R, Bridle KR, Crawford DHG, Jayachandran A, et al. Spotlight on Bortezomib: potential in the treatment of hepatocellular carcinoma. Expert Opin Investig Drugs. 2019;28(1):7–18.
Article
CAS
PubMed
Google Scholar
Augello G, Modica M, Azzolina A, Puleio R, Cassata G, Emma MR, et al. Preclinical evaluation of antitumor activity of the proteasome inhibitor MLN2238 (ixazomib) in hepatocellular carcinoma cells. Cell Death Dis. 2018;9(2):28.
Article
PubMed
PubMed Central
CAS
Google Scholar
Ciombor KK, Feng Y, Benson AB 3rd, Su Y, Horton L, Short SP, et al. Phase II trial of bortezomib plus doxorubicin in hepatocellular carcinoma (E6202): a trial of the eastern cooperative oncology group. Investig New Drugs. 2014;32(5):1017–27.
Article
CAS
Google Scholar
Zhu AX, Rosmorduc O, Evans TRJ, Ross PJ, Santoro A, Carrilho FJ, et al. SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2014;33(6):559–66.
Article
PubMed
CAS
Google Scholar
Abou-Alfa GK, Shi Q, Knox JJ, Kaubisch A, Niedzwiecki D, Posey J, et al. Assessment of treatment with sorafenib plus doxorubicin vs sorafenib alone in patients with advanced hepatocellular carcinoma: phase 3 CALGB 80802 randomized clinical trial. JAMA Oncol. 2019;5(11):1582–8.
Article
PubMed
PubMed Central
Google Scholar
Kudo M, Ueshima K, Yokosuka O, Ogasawara S, Obi S, Izumi N, et al. Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): a randomised, open label, phase 3 trial. Lancet Gastroenterol Hepatol. 2018;3(6):424–32.
Article
PubMed
Google Scholar
Llovet JM, Hernandez-Gea V. Hepatocellular carcinoma: reasons for phase III failure and novel perspectives on trial design. Clin Cancer Res. 2014;20(8):2072–9.
Article
CAS
PubMed
Google Scholar
Rashid MBMA, Toh TB, Hooi L, Silva A, Zhang Y, Tan PF, et al. Optimizing drug combinations against multiple myeloma using a quadratic phenotypic optimization platform (QPOP). Sci Transl Med. 2018;10(453):eaan0941.
Article
PubMed
CAS
Google Scholar
Zarrinpar A, Lee D-K, Silva A, Datta N, Kee T, Eriksen C, et al. Individualizing liver transplant immunosuppression using a phenotypic personalized medicine platform. Sci Transl Med. 2016;8(333):333ra49.
Article
PubMed
CAS
Google Scholar
Wang H, Lee DK, Chen KY, Chen JY, Zhang K, Silva A, et al. Mechanism-independent optimization of combinatorial nanodiamond and unmodified drug delivery using a phenotypically driven platform technology. ACS Nano. 2015;9(3):3332–44.
Article
CAS
PubMed
Google Scholar
Blasiak A, Lim JJ, Seah SGK, Kee T, Remus A, Chye H, et al. IDentif.AI: rapidly optimizing combination therapy design against severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) with digital drug development. Bioeng Transl Med. 2021;6(1):e10196.
Article
CAS
PubMed
Google Scholar
Lee BY, Clemens DL, Silva A, Dillon BJ, Masleša-Galić S, Nava S, et al. Drug regimens identified and optimized by output-driven platform markedly reduce tuberculosis treatment time. Nat Commun. 2017;8:14183.
Article
CAS
PubMed
PubMed Central
Google Scholar
de Mel S, Rashid MBM, Zhang XY, Goh J, Lee CT, Poon LM, et al. Application of an ex-vivo drug sensitivity platform towards achieving complete remission in a refractory T-cell lymphoma. Blood Cancer J. 2020;10(1):9.
Article
PubMed
PubMed Central
Google Scholar
Friedman AA, Letai A, Fisher DE, Flaherty KT. Precision medicine for cancer with next-generation functional diagnostics. Nat Rev Cancer. 2015;15(12):747–56.
Article
CAS
PubMed
PubMed Central
Google Scholar
Broutier L, Mastrogiovanni G, Verstegen MMA, Francies HE, Gavarró LM, Bradshaw CR, et al. Human primary liver cancer–derived organoid cultures for disease modeling and drug screening. Nat Med. 2017;23(12):1424–35.
Article
CAS
PubMed
PubMed Central
Google Scholar
Tentler JJ, Tan AC, Weekes CD, Jimeno A, Leong S, Pitts TM, et al. Patient-derived tumour xenografts as models for oncology drug development. Nat Rev Clin Oncol. 2012;9(6):338–50.
Article
CAS
PubMed
PubMed Central
Google Scholar
Fong ELS, Toh TB, Lin QXX, Liu Z, Hooi L, Mohd Abdul Rashid MB, et al. Generation of matched patient-derived xenograft in vitro-in vivo models using 3D macroporous hydrogels for the study of liver cancer. Biomaterials. 2018;159:229–40.
Article
CAS
PubMed
Google Scholar
Broutier L, Andersson-Rolf A, Hindley CJ, Boj SF, Clevers H, Koo B-K, et al. Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation. Nat Protoc. 2016;11(9):1724–43.
Article
CAS
PubMed
Google Scholar
Xu H, Jaynes J, Ding X. Combining two-level and three-level orthogonal arrays for factor screening and response surface exploration. Stat Sin. 2014;24:269–89.
Google Scholar
Chou T-C. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006;58(3):621–81.
Article
CAS
PubMed
Google Scholar
Veldman-Jones MH, Brant R, Rooney C, Geh C, Emery H, Harbron CG, et al. Evaluating robustness and sensitivity of the NanoString technologies nCounter platform to enable multiplexed gene expression analysis of clinical samples. Cancer Res. 2015;75(13):2587–93.
Article
CAS
PubMed
Google Scholar
Parry D, Guzi T, Shanahan F, Davis N, Prabhavalkar D, Wiswell D, et al. Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor. Mol Cancer Ther. 2010;9(8):2344–53.
Article
CAS
PubMed
Google Scholar
Kirk CJ. Discovery and development of second-generation proteasome inhibitors. Semin Hematol. 2012;49(3):207–14.
Article
CAS
PubMed
Google Scholar
Dick LR, Fleming PE. Building on bortezomib: second-generation proteasome inhibitors as anti-cancer therapy. Drug Discov Today. 2010;15(5):243–9.
Article
CAS
PubMed
Google Scholar
Qin S, Bai Y, Lim HY, Thongprasert S, Chao Y, Fan J, et al. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol. 2013;31(28):3501–8.
Article
CAS
PubMed
Google Scholar
Qin S, Cheng Y, Liang J, Shen L, Bai Y, Li J, et al. Efficacy and safety of the FOLFOX4 regimen versus doxorubicin in Chinese patients with advanced hepatocellular carcinoma: a subgroup analysis of the EACH study. Oncologist. 2014;19(11):1169–78.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lyu N, Kong Y, Mu L, Lin Y, Li J, Liu Y, et al. Hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin vs. sorafenib for advanced hepatocellular carcinoma. J Hepatol. 2018;69(1):60–9.
Article
PubMed
CAS
Google Scholar
Lee A-H, Iwakoshi NN, Anderson KC, Glimcher LH. Proteasome inhibitors disrupt the unfolded protein response in myeloma cells. Proc Natl Acad Sci U S A. 2003;100(17):9946–51.
Article
CAS
PubMed
PubMed Central
Google Scholar
Jiang H-Y, Wek RC. Phosphorylation of the α-subunit of the eukaryotic initiation factor-2 (eIF2α) reduces protein synthesis and enhances apoptosis in response to proteasome inhibition. J Biol Chem. 2005;280(14):14189–202.
Article
CAS
PubMed
Google Scholar
Ri M. Endoplasmic-reticulum stress pathway-associated mechanisms of action of proteasome inhibitors in multiple myeloma. Int J Hematol. 2016;104(3):273–80.
Article
CAS
PubMed
Google Scholar
Obeng EA, Carlson LM, Gutman DM, Harrington WJ Jr, Lee KP, Boise LH. Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood. 2006;107(12):4907–16.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wortel IMN, van der Meer LT, Kilberg MS, van Leeuwen FN. Surviving stress: modulation of ATF4-mediated stress responses in normal and malignant cells. Trends Endocrinol Metab. 2017;28(11):794–806.
Article
CAS
PubMed
PubMed Central
Google Scholar
Nawrocki ST, Carew JS, Pino MS, Highshaw RA, Andtbacka RHI, Dunner K, et al. Aggresome disruption: a novel strategy to enhance bortezomib-induced apoptosis in pancreatic cancer cells. Cancer Res. 2006;66(7):3773–81.
Article
CAS
PubMed
Google Scholar
Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao T-P. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell. 2003;115(6):727–38.
Article
CAS
PubMed
Google Scholar
Hideshima T, Bradner JE, Wong J, Chauhan D, Richardson P, Schreiber SL, et al. Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma. Proc Natl Acad Sci U S A. 2005;102(24):8567.
Article
CAS
PubMed
PubMed Central
Google Scholar
Chauhan D, Tian Z, Zhou B, Kuhn D, Orlowski R, Raje N, et al. In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clin Cancer Res. 2011;17(16):5311–21.
Article
CAS
PubMed
PubMed Central
Google Scholar
Engür S, Dikmen M. The evaluation of the anti-cancer activity of ixazomib on Caco2 colon solid tumor cells, comparison with bortezomib. Acta Clin Belg. 2017;72(6):391–8.
Article
PubMed
Google Scholar
Lin S-F, Lin J-D, Hsueh C, Chou T-C, Wong RJ. A cyclin-dependent kinase inhibitor, dinaciclib in preclinical treatment models of thyroid cancer. Plos One. 2017;12(2):e0172315.
Article
PubMed
PubMed Central
CAS
Google Scholar
Hayakawa J, Mittal S, Wang Y, Korkmaz KS, Adamson E, English C, et al. Identification of promoters bound by c-Jun/ATF2 during rapid large-scale gene activation following genotoxic stress. Mol Cell. 2004;16(4):521–35.
Article
CAS
PubMed
Google Scholar
Tournier C, Hess P, Yang DD, Xu J, Turner TK, Nimnual A, et al. Requirement of JNK for stress- induced activation of the cytochrome c-mediated death pathway. Science. 2000;288(5467):870.
Article
CAS
PubMed
Google Scholar
Dhanasekaran DN, Reddy EP. JNK signaling in apoptosis. Oncogene. 2008;27(48):6245–51.
Article
CAS
PubMed
PubMed Central
Google Scholar
Dhanasekaran DN, Reddy EP. JNK-signaling: a multiplexing hub in programmed cell death. Genes Cancer. 2017;8(9–10):682–94.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bruix J, Gores GJ, Mazzaferro V. Hepatocellular carcinoma: clinical frontiers and perspectives. Gut. 2014;63(5):844–55.
Article
CAS
PubMed
Google Scholar
Huang D, Lim JQ, Cheah DMZ, Kahliab K, Laurensia Y, Pang JWL, et al. Whole-genome sequencing reveals potent therapeutic strategy for monomorphic epitheliotropic intestinal T-cell lymphoma. Blood Adv. 2020;4(19):4769–74.
Article
CAS
PubMed
PubMed Central
Google Scholar
Tang H, Xu L, Cen X, Yang L, Feng J, Li G, et al. CDK5 inhibition in vitro and in vivo induces cell death in myeloma and overcomes the obstacle of bortezomib resistance. Int J Mol Med. 2020;45(6):1661–72.
CAS
PubMed
PubMed Central
Google Scholar
Saqub H, Proetsch-Gugerbauer H, Bezrookove V, Nosrati M, Vaquero EM, de Semir D, et al. Dinaciclib, a cyclin-dependent kinase inhibitor, suppresses cholangiocarcinoma growth by targeting CDK2/5/9. Sci Rep. 2020;10(1):18489.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bates DJ, Salerni BL, Lowrey CH, Eastman A. Vinblastine sensitizes leukemia cells to cyclin-dependent kinase inhibitors, inducing acute cell cycle phase-independent apoptosis. Cancer Biol Ther. 2011;12(4):314–25.
Article
CAS
PubMed
PubMed Central
Google Scholar
Howard D, James D, Murphy K, Garcia-Parra J, Pan-Castillo B, Rex S, et al. Dinaciclib, a bimodal agent effective against endometrial cancer. Cancers (Basel). 2021;13(5):1135.
Article
CAS
Google Scholar
Chen Z, Wang Z, Pang JC, Yu Y, Bieerkehazhi S, Lu J, et al. Multiple CDK inhibitor dinaciclib suppresses neuroblastoma growth via inhibiting CDK2 and CDK9 activity. Sci Rep. 2016;6(1):29090.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wang H, Yu Y, Jiang Z, Cao W-M, Wang Z, Dou J, et al. Next-generation proteasome inhibitor MLN9708 sensitizes breast cancer cells to doxorubicin-induced apoptosis. Sci Rep. 2016;6(1):26456.
Article
CAS
PubMed
PubMed Central
Google Scholar
Broux M, Prieto C, Demeyer S, Vanden Bempt M, Alberti-Servera L, Lodewijckx I, et al. Suz12 inactivation cooperates with JAK3 mutant signaling in the development of T-cell acute lymphoblastic leukemia. Blood. 2019;134(16):1323–36.
Article
CAS
PubMed
PubMed Central
Google Scholar
Song Y, Kim I-K, Choi I, Kim S-H, Seo HR. Oxytetracycline have the therapeutic efficiency in CD133(+) HCC population through suppression CD133 expression by decreasing of protein stability of CD133. Sci Rep. 2018;8(1):16100.
Article
PubMed
PubMed Central
CAS
Google Scholar
Nam HJ, Kim YE, Moon B-S, Kim HY, Jung D, Choi S, et al. Azathioprine antagonizes aberrantly elevated lipid metabolism and induces apoptosis in glioblastoma. iScience. 2021;24(3):102238.
Article
CAS
PubMed
PubMed Central
Google Scholar
Zhan T, Ambrosi G, Wandmacher AM, Rauscher B, Betge J, Rindtorff N, et al. MEK inhibitors activate Wnt signalling and induce stem cell plasticity in colorectal cancer. Nat Commun. 2019;10(1):2197.
Article
PubMed
PubMed Central
CAS
Google Scholar
Zhang Q, Lou Y, Yang J, Wang J, Feng J, Zhao Y, et al. Integrated multiomic analysis reveals comprehensive tumour heterogeneity and novel immunophenotypic classification in hepatocellular carcinomas. Gut. 2019;68(11):2019–31.
Article
CAS
PubMed
Google Scholar
Ding X, He M, Chan AWH, Song QX, Sze SC, Chen H, et al. Genomic and epigenomic features of primary and recurrent hepatocellular carcinomas. Gastroenterology. 2019;157(6):1630–45.e6.
Article
CAS
PubMed
Google Scholar