REFERENCES
1. Kozalak G, Bütün İ, Toyran E, Koşar A. Review on Bortezomib resistance in multiple myeloma and potential role of emerging technologies. Pharmaceuticals 2023;16:111.
2. Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol 2020;95:548-67.
3. Yang T, Liu X, Kumar SK, Jin F, Dai Y. Decoding DNA methylation in epigenetics of multiple myeloma. Blood Rev 2022;51:100872.
4. Gkoliou G, Agathangelidis A, Karakatsoulis G, et al. Differences in the immunoglobulin gene repertoires of IgG versus IgA multiple myeloma allude to distinct immunopathogenetic trajectories. Front Oncol 2023;13:1123029.
5. Ho M, Patel A, Hanley C, et al. Exploiting autophagy in multiple myeloma. J Cancer Metastasis Treat 2019;5:70.
6. Mateos MV, Ludwig H, Bazarbachi A, et al. Insights on multiple myeloma treatment strategies. Hemasphere 2019;3:e163.
7. Pinto V, Bergantim R, Caires HR, Seca H, Guimarães JE, Vasconcelos MH. Multiple myeloma: available therapies and causes of drug resistance. Cancers 2020;12:407.
8. Galluzzi L, Vitale I, Aaronson SA, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 2018;25:486-541.
9. Yan G, Elbadawi M, Efferth T. Multiple cell death modalities and their key features (Review). World Acad Sci J 2020;2:39-48.
11. Bertheloot D, Latz E, Franklin BS. Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cell Mol Immunol 2021;18:1106-21.
12. Newton K, Wickliffe KE, Dugger DL, et al. Cleavage of RIPK1 by caspase-8 is crucial for limiting apoptosis and necroptosis. Nature 2019;574:428-31.
13. Degenhardt K, Mathew R, Beaudoin B, et al. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 2006;10:51-64.
14. Yun Z, Zhichao J, Hao Y, et al. Targeting autophagy in multiple myeloma. Leuk Res 2017;59:97-104.
15. Carroll RG, Martin SJ. Autophagy in multiple myeloma: what makes you stronger can also kill you. Cancer Cell 2013;23:425-6.
16. Bashiri H, Tabatabaeian H. Autophagy: a potential therapeutic target to tackle drug resistance in multiple myeloma. Int J Mol Sci 2023;24:6019.
17. Aquila S, Santoro M, Caputo A, Panno ML, Pezzi V, De Amicis F. The tumor suppressor PTEN as molecular switch node regulating cell metabolism and autophagy: implications in immune system and tumor microenvironment. Cells 2020;9:1725.
18. Al-Odat OS, Guirguis DA, Schmalbach NK, et al. Autophagy and apoptosis: current challenges of treatment and drug resistance in multiple myeloma. Int J Mol Sci 2022;24:644.
19. Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol 2010;221:3-12.
20. Song Y, Quach C, Liang C. UVRAG in autophagy, inflammation, and cancer. Autophagy 2020;16:387-8.
21. Aman Y, Schmauck-Medina T, Hansen M, et al. Autophagy in healthy aging and disease. Nat Aging 2021;1:634-50.
22. Jaganathan S, Malek E, Vallabhapurapu S, Vallabhapurapu S, Driscoll JJ. Bortezomib induces AMPK-dependent autophagosome formation uncoupled from apoptosis in drug resistant cells. Oncotarget 2014;5:12358-70.
23. Nikesitch N, Lee JM, Ling S, Roberts TL. Endoplasmic reticulum stress in the development of multiple myeloma and drug resistance. Clin Transl Immunology 2018;7:e1007.
24. Harmon KA, Roman S, Lancaster HD, et al. Structural and ultrastructural analysis of the multiple myeloma cell niche and a patient-specific model of plasma cell dysfunction. Microsc Microanal 2022;28:254-64.
25. Jung G, Roh J, Lee H, et al. Autophagic markers BECLIN 1 and LC3 are associated with prognosis of multiple myeloma. Acta Haematol 2015;134:17-24.
26. Puglisi F, Parrinello NL, Giallongo C, et al. Plasticity of high-density neutrophils in multiple myeloma is associated with increased autophagy via STAT3. Int J Mol Sci 2019;20:3548.
27. Clavero E, Sanchez-Maldonado JM, Macauda A, et al. Polymorphisms within autophagy-related genes as susceptibility biomarkers for multiple myeloma: a meta-analysis of three large cohorts and functional characterization. Int J Mol Sci 2023;24:8500.
29. Kumar AV, Mills J, Lapierre LR. Selective autophagy receptor p62/SQSTM1, a pivotal player in stress and aging. Front Cell Dev Biol 2022;10:793328.
30. Milan E, Perini T, Resnati M, et al. A plastic SQSTM1/p62-dependent autophagic reserve maintains proteostasis and determines proteasome inhibitor susceptibility in multiple myeloma cells. Autophagy 2015;11:1161-78.
31. Auner HW, Cenci S. Recent advances and future directions in targeting the secretory apparatus in multiple myeloma. Br J Haematol 2015;168:14-25.
32. Conway KL, Kuballa P, Khor B, et al. ATG5 regulates plasma cell differentiation. Autophagy 2013;9:528-37.
33. Pengo N, Scolari M, Oliva L, et al. Plasma cells require autophagy for sustainable immunoglobulin production. Nat Immunol 2013;14:298-305.
34. 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;107:4907-16.
35. Borjan B, Kern J, Steiner N, Gunsilius E, Wolf D, Untergasser G. Spliced XBP1 levels determine sensitivity of multiple myeloma cells to proteasome inhibitor Bortezomib independent of the unfolded protein response mediator GRP78. Front Oncol 2019;9:1530.
36. Adams CJ, Kopp MC, Larburu N, Nowak PR, Ali MMU. Structure and molecular mechanism of ER stress signaling by the unfolded protein response signal activator IRE1. Front Mol Biosci 2019;6:11.
37. Cairrão F, Santos CC, Le Thomas A, Marsters S, Ashkenazi A, Domingos PM. Pumilio protects Xbp1 mRNA from regulated Ire1-dependent decay. Nat Commun 2022;13:1587.
38. Zheng W, Xie W, Yin D, Luo R, Liu M, Guo F. ATG5 and ATG7 induced autophagy interplays with UPR via PERK signaling. Cell Commun Signal 2019;17:42.
39. Park SM, Kang TI, So JS. Roles of XBP1s in transcriptional regulation of target genes. Biomedicines 2021;9:791.
40. Harnoss JM, Le Thomas A, Shemorry A, et al. Disruption of IRE1α through its kinase domain attenuates multiple myeloma. Proc Natl Acad Sci U S A 2019;116:16420-9.
41. Mimura N, Fulciniti M, Gorgun G, et al. Blockade of XBP1 splicing by inhibition of IRE1α is a promising therapeutic option in multiple myeloma. Blood 2012;119:5772-81.
42. Dang J, Bian X, Ma X, et al. ORMDL3 facilitates the survival of splenic B cells via an ATF6α-endoplasmic reticulum stress-Beclin1 autophagy regulatory pathway. J Immunol 2017;199:1647-59.
43. Sharma RB, Darko C, Alonso LC. Intersection of the ATF6 and XBP1 ER stress pathways in mouse islet cells. J Biol Chem 2020;295:14164-77.
44. Sintes J, Gentile M, Zhang S, et al. mTOR intersects antibody-inducing signals from TACI in marginal zone B cells. Nat Commun 2017;8:1462.
45. Hu R, Warri A, Jin L, et al. NF-κB signaling is required for XBP1 (unspliced and spliced)-mediated effects on antiestrogen responsiveness and cell fate decisions in breast cancer. Mol Cell Biol 2015;35:379-90.
46. Verzella D, Pescatore A, Capece D, et al. Life, death, and autophagy in cancer: NF-κB turns up everywhere. Cell Death Dis 2020;11:210.
47. Shi Z, Yu X, Yuan M, et al. Activation of the PERK-ATF4 pathway promotes chemo-resistance in colon cancer cells. Sci Rep 2019;9:3210.
48. Jang JE, Eom JI, Jeung HK, et al. PERK/NRF2 and autophagy form a resistance mechanism against G9a inhibition in leukemia stem cells. J Exp Clin Cancer Res 2020;39:66.
49. White-Gilbertson S, Hua Y, Liu B. The role of endoplasmic reticulum stress in maintaining and targeting multiple myeloma: a double-edged sword of adaptation and apoptosis. Front Genet 2013;4:109.
50. Michallet AS, Mondiere P, Taillardet M, Leverrier Y, Genestier L, Defrance T. Compromising the unfolded protein response induces autophagy-mediated cell death in multiple myeloma cells. PLoS One 2011;6:e25820.
51. Bagratuni T, Patseas D, Mavrianou-Koutsoukou N, et al. Characterization of a PERK kinase inhibitor with anti-myeloma activity. Cancers 2020;12:2864.
52. Allegra A, Casciaro M, Barone P, Musolino C, Gangemi S. Epigenetic crosstalk between malignant plasma cells and the tumour microenvironment in multiple myeloma. Cancers 2022;14:2597.
53. Cippitelli M, Stabile H, Kosta A, et al. Role of NF-κB signaling in the interplay between multiple myeloma and mesenchymal stromal cells. Int J Mol Sci 2023;24:1823.
54. Gu J, Huang X, Zhang Y, Bao C, Zhou Z, Jin J. Cytokine profiles in patients with newly diagnosed multiple myeloma: survival is associated with IL-6 and IL-17A levels. Cytokine 2021;138:155358.
55. Sanchez E, Gillespie A, Tang G, et al. Soluble B-cell maturation antigen mediates tumor-induced immune deficiency in multiple myeloma. Clin Cancer Res 2016;22:3383-97.
56. Yan Y, Chen X, Wang X, et al. The effects and the mechanisms of autophagy on the cancer-associated fibroblasts in cancer. J Exp Clin Cancer Res 2019;38:171.
57. Frassanito MA, De Veirman K, Desantis V, et al. Halting pro-survival autophagy by TGFβ inhibition in bone marrow fibroblasts overcomes bortezomib resistance in multiple myeloma patients. Leukemia 2016;30:640-8.
58. Liu Z, Xu J, He J, et al. Mature adipocytes in bone marrow protect myeloma cells against chemotherapy through autophagy activation. Oncotarget 2015;6:34329-41.
59. Cea M, Cagnetta A, Fulciniti M, et al. Targeting NAD+ salvage pathway induces autophagy in multiple myeloma cells via mTORC1 and extracellular signal-regulated kinase (ERK1/2) inhibition. Blood 2012;120:3519-29.
60. Spaan I, Raymakers RA, van de Stolpe A, Peperzak V. Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential. J Hematol Oncol 2018;11:67.
61. Liu YS, Liu XB, Qiu YY, Lan T, Chen Y. Molecular mechanism of Wnt signal pathway in multiple myeloma cell line H929 cell autophagy. Eur Rev Med Pharmacol Sci 2018;22:3327-32.
62. Pereira IEG, da Costa Cacemiro M, Cominal JG, Barretto GD, de Castro FA. Role of endothelial cells in hematological malignancies. EJMO 2022;6:210-8.
63. Tenreiro MM, Correia ML, Brito MA. Endothelial progenitor cells in multiple myeloma neovascularization: a brick to the wall. Angiogenesis 2017;20:443-62.
64. Wang X, Zhang Z, Yao C. Angiogenic activity of mesenchymal stem cells in multiple myeloma. Cancer Invest 2011;29:37-41.
65. Rao L, Giannico D, Leone P, et al. HB-EGF-EGFR signaling in bone marrow endothelial cells mediates angiogenesis associated with multiple myeloma. Cancers 2020;12:173.
66. Di Lernia G, Leone P, Solimando AG, et al. Bortezomib treatment modulates autophagy in multiple myeloma. J Clin Med 2020;9:552.
67. Muz B, Azab F, De La Puente P, Ghobrial IM, Vij R, Azab AK. Hypoxia induces drug resistance in multiple myeloma. Blood 2013;122:1852.
68. Lamy L, Ngo VN, Emre NCT, et al. Control of autophagic cell death by caspase-10 in multiple myeloma. Cancer Cell 2013;23:435-49.
69. Kozalak G, Öksüzoğlu E. Efficacy of multi-drug resistance transporters and glutathione S-transferase P-1 at developing bortezomib resistance in multiple myeloma cell lines. Lat Am J Pharm 2021;40:2709-16. Available from: https://www.latamjpharm.org/resumenes/40/11/LAJOP_40_11_1_23.pdf. [Last accessed on 22 Dec 2023]
70. Milani M, Rzymski T, Mellor HR, et al. The role of ATF4 stabilization and autophagy in resistance of breast cancer cells treated with Bortezomib. Cancer Res 2009;69:4415-23.
71. Nikesitch N, Rebeiro P, Ho LL, et al. The role of chaperone-mediated autophagy in Bortezomib resistant multiple myeloma. Cells 2021;10:3464.
72. Lu Y, Wang Y, Xu H, Shi C, Jin F, Li W. Profilin 1 induces drug resistance through Beclin1 complex-mediated autophagy in multiple myeloma. Cancer Sci 2018;109:2706-16.
73. Zhang M, He J, Liu Z, et al. Anti-β2-microglobulin monoclonal antibodies overcome bortezomib resistance in multiple myeloma by inhibiting autophagy. Oncotarget 2015;6:8567-78.
74. Huang X, Cao W, Yao S, et al. NEDD4L binds the proteasome and promotes autophagy and bortezomib sensitivity in multiple myeloma. Cell Death Dis 2022;13:197.
75. Xia J, He Y, Meng B, et al. NEK2 induces autophagy-mediated bortezomib resistance by stabilizing Beclin-1 in multiple myeloma. Mol Oncol 2020;14:763-78.
76. Abdel Malek MAY, Jagannathan S, Malek E, et al. Molecular chaperone GRP78 enhances aggresome delivery to autophagosomes to promote drug resistance in multiple myeloma. Oncotarget 2015;6:3098-110.
77. Wu H, Liu C, Yang Q, et al. MIR145-3p promotes autophagy and enhances bortezomib sensitivity in multiple myeloma by targeting HDAC4. Autophagy 2020;16:683-97.
78. Tucci M, Stucci S, Savonarola A, et al. An imbalance between Beclin-1 and p62 expression promotes the proliferation of myeloma cells through autophagy regulation. Exp Hematol 2014;42:897-908.e1.
79. Sola B, Poirot M, de Medina P, et al. Antiestrogen-binding site ligands induce autophagy in myeloma cells that proceeds through alteration of cholesterol metabolism. Oncotarget 2013;4:911-22.
80. Riz I, Hawley TS, Hawley RG. KLF4-SQSTM1/p62-associated prosurvival autophagy contributes to carfilzomib resistance in multiple myeloma models. Oncotarget 2015;6:14814-31.
81. Pan YZ, Wang X, Bai H, Wang CB, Zhang Q, Xi R. Autophagy in drug resistance of the multiple myeloma cell line RPMI8226 to doxorubicin. Genet Mol Res 2015;14:5621-9.
82. Bellot G, Garcia-Medina R, Gounon P, et al. Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol 2009;29:2570-81.
83. Papandreou I, Lim AL, Laderoute K, Denko NC. Hypoxia signals autophagy in tumor cells via AMPK activity, independent of HIF-1, BNIP3, and BNIP3L. Cell Death Differ 2008;15:1572-81.
84. Gastelum G, Veena M, Lyons K, et al. Can targeting hypoxia-mediated acidification of the bone marrow microenvironment kill myeloma tumor cells? Front Oncol 2021;11:703878.
85. Ikeda S, Tagawa H. Impact of hypoxia on the pathogenesis and therapy resistance in multiple myeloma. Cancer Sci 2021;112:3995-4004.
86. Infantino V, Santarsiero A, Convertini P, Todisco S, Iacobazzi V. Cancer cell metabolism in hypoxia: role of HIF-1 as key regulator and therapeutic target. Int J Mol Sci 2021;22:5703.
87. Ikeda S, Abe F, Matsuda Y, Kitadate A, Takahashi N, Tagawa H. Hypoxia-inducible hexokinase-2 enhances anti-apoptotic function via activating autophagy in multiple myeloma. Cancer Sci 2020;111:4088-101.
88. Bhaskar A, Tiwary BN. Hypoxia inducible factor-1 alpha and multiple myeloma. Int J Adv Res 2016;4:706-15.
89. Darawshi O, Muz B, Naamat SG, et al. An mTORC1 to HRI signaling axis promotes cytotoxicity of proteasome inhibitors in multiple myeloma. Cell Death Dis 2022;13:969.
90. Eliopoulos AG, Havaki S, Gorgoulis VG. DNA damage response and autophagy: a meaningful partnership. Front Genet 2016;7:204.
91. Alexander A, Kim J, Walker CL. ATM engages the TSC2/mTORC1 signaling node to regulate autophagy. Autophagy 2010;6:672-3.
92. Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 2011;13:132-41.
93. Desantis A, Bruno T, Catena V, et al. Che-1-induced inhibition of mTOR pathway enables stress-induced autophagy. EMBO J 2015;34:1214-30.
94. Kim JS, Ro SH, Kim M, et al. Sestrin2 inhibits mTORC1 through modulation of GATOR complexes. Sci Rep 2015;5:9502.
95. Copetti T, Bertoli C, Dalla E, Demarchi F, Schneider C. p65/RelA modulates BECN1 transcription and autophagy. Mol Cell Biol 2009;29:2594-608.
96. Rodríguez-Vargas JM, Ruiz-Magaña MJ, Ruiz-Ruiz C, et al. ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy. Cell Res 2012;22:1181-98.
97. Feng Z, Hu W, de Stanchina E, et al. The regulation of AMPK β1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways. Cancer Res 2007;67:3043-53.
98. Eisenberg-Lerner A, Kimchi A. PKD is a kinase of Vps34 that mediates ROS-induced autophagy downstream of DAPk. Cell Death Differ 2012;19:788-97.
99. Wang L, Zhang H, Sun M, Yin Z, Qian J. High mobility group box 1-mediated autophagy promotes neuroblastoma cell chemoresistance. Oncol Rep 2015;34:2969-76.
100. Guo X, He D, Zhang E, et al. HMGB1 knockdown increases MM cell vulnerability by regulating autophagy and DNA damage repair. J Exp Clin Cancer Res 2018;37:205.
101. Roy M, Liang L, Xiao X, et al. Lycorine downregulates HMGB1 to inhibit autophagy and enhances Bortezomib activity in multiple myeloma. Theranostics 2016;6:2209-24.
102. Gao D, Lv AE, Li HP, Han DH, Zhang YP. LncRNA MALAT-1 elevates HMGB1 to promote autophagy resulting in inhibition of tumor cell apoptosis in multiple myeloma. J Cell Biochem 2017;118:3341-8.
103. Balsas P, López-Royuela N, Galán-Malo P, Anel A, Marzo I, Naval J. Cooperation between Apo2L/TRAIL and Bortezomib in multiple myeloma apoptosis. Biochem Pharmacol 2009;77:804-12.
104. Al-Odat O, von Suskil M, Chitren RJ, et al. Mcl-1 inhibition: managing malignancy in multiple myeloma. Front Pharmacol 2021;12:699629.
105. Öksüzoğlu E, Kozalak G. Inhibition of apoptosis may lead to the development of bortezomib resistance in multiple myeloma cancer cells. Turkish J Biochem 2021;46:65-71.
106. Roy P, Sarkar UA, Basak S. The NF-κB activating pathways in multiple myeloma. Biomedicines 2018;6:59.
107. Hoang B, Benavides A, Shi Y, Frost P, Lichtenstein A. Effect of autophagy on multiple myeloma cell viability. Mol Cancer Ther 2009;8:1974-84.
108. Zeng R, Chen Y, Zhao S, Cui GH. Autophagy counteracts apoptosis in human multiple myeloma cells exposed to oridonin in vitro via regulating intracellular ROS and SIRT1. Acta Pharmacol Sin 2012;33:91-100.
109. Strappazzon F, Vietri-Rudan M, Campello S, et al. Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy. EMBO J 2011;30:1195-208.
110. Sun WL. Ambra1 in autophagy and apoptosis: implications for cell survival and chemotherapy resistance. Oncol Lett 2016;12:367-74.
111. Mohammadi K, Salimi M, Angaji SA, Saniotis A, Mahjoobi F. Association study of Bif-1 gene expression with histopathological characteristics and hormone receptors in breast cancer. BMC Womens Health 2022;22:471.
112. Sui X, Kong N, Ye L, et al. p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents. Cancer Lett 2014;344:174-9.
114. Ramakrishnan V, Kumar S. PI3K/AKT/mTOR pathway in multiple myeloma: from basic biology to clinical promise. Leuk Lymphoma 2018;59:2524-34.
115. Fu YF, Liu X, Gao M, Zhang YN, Liu J. Endoplasmic reticulum stress induces autophagy and apoptosis while inhibiting proliferation and drug resistance in multiple myeloma through the PI3K/Akt/mTOR signaling pathway. Oncotarget 2017;8:61093-106.
116. Jin Z, Li Y, Pitti R, et al. Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling. Cell 2009;137:721-35.
117. Manfrini N, Mancino M, Miluzio A, et al. FAM46C and FNDC3A are multiple myeloma tumor suppressors that act in concert to impair clearing of protein aggregates and autophagy. Cancer Res 2020;80:4693-706.
118. Fucci C, Resnati M, Riva E, et al. The interaction of the tumor suppressor FAM46C with p62 and FNDC3 proteins integrates protein and secretory homeostasis. Cell Rep 2020;32:108162.
119. Wu Z, Wu L, Zou L, Wang M, Liu X. Metformin induces myeloma cells necrosis and apoptosis and it is considered for therapeutic use. J Chemother 2023;35:131-41.
120. Jagannathan S, Abdel-Malek MAY, Malek E, et al. Pharmacologic screens reveal metformin that suppresses GRP78-dependent autophagy to enhance the anti-myeloma effect of bortezomib. Leukemia 2015;29:2184-91.
121. Wang Y, Xu W, Yan Z, et al. Metformin induces autophagy and G0/G1 phase cell cycle arrest in myeloma by targeting the AMPK/mTORC1 and mTORC2 pathways. J Exp Clin Cancer Res 2018;37:63.
122. Hibino S, Eto S, Hangai S et al. Tumor cell-derived spermidine is an oncometabolite that suppresses TCR clustering for intratumoral CD8+ T cell activation. Proc Natl Acad Sci U S A 2023;120:e2305245120.
123. Ma R, Yu D, Peng Y, et al. Resveratrol induces AMPK and mTOR signaling inhibition-mediated autophagy and apoptosis in multiple myeloma cells. Acta Biochim Biophys Sin 2021;53:775-83.
124. Jin HG, Wu GZ, Wu GH, Bao YG. Combining the mammalian target of rapamycin inhibitor, rapamycin, with resveratrol has a synergistic effect in multiple myeloma. Oncol Lett 2018;15:6257-64.
125. Wang G, Zhou P, Chen X, et al. The novel autophagy inhibitor elaiophylin exerts antitumor activity against multiple myeloma with mutant TP53 in part through endoplasmic reticulum stress-induced apoptosis. Cancer Biol Ther 2017;18:584-95.
126. Wu CH, Ou CH, Yen IC, Lee SY. 4-acetylantroquinonol B inhibits osteoclastogenesis by inhibiting the autophagy pathway in a simulated microgravity model. Int J Mol Sci 2020;21:6971.
127. Li N, Zhang X, Chen J, Gao S, Wang L, Zhao Y. Perturbation of autophagy by a Beclin 1-targeting stapled peptide induces mitochondria stress and inhibits proliferation of pancreatic cancer cells. Cancers 2023;15:953.
128. Ailawadhi S, Parrondo RD, Moustafa MA, et al. Ibrutinib, lenalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma: phase I trial results. Hematol Oncol 2022;40:695-703.
129. Domenger A, Choisy C, Baron L, et al. The Sec61 translocon is a therapeutic vulnerability in multiple myeloma. EMBO Mol Med 2022;14:e14740.
130. Shi Y, Yang Y, Hoang B, et al. Retracted article: Therapeutic potential of targeting IRES-dependent c-myc translation in multiple myeloma cells during ER stress. Oncogene 2016;35:1015-24.
131. Suder A. Final results of phase I study of the oral class I PI3K inhibitor CH5132799 in patients with advanced solid tumours. Ann Oncol 2013;24:i33.
132. Kikuchi H, Amofa E, Mcenery M, et al. Inhibition of PI3K class IA kinases using GDC-0941 overcomes cytoprotection of multiple myeloma cells in the osteoclastic bone marrow microenvironment enhancing the efficacy of current clinical therapeutics. Cancers 2023;15:462.
133. Attar-Schneider O, Drucker L, Zismanov V, Tartakover-Matalon S, Rashid G, Lishner M. Bevacizumab attenuates major signaling cascades and eIF4E translation initiation factor in multiple myeloma cells. Lab Invest 2012;92:178-90.
134. Wang JZ, Chen JM, Zeng ZY, Qiu DB. [Effects of autophagy regulating drugs on proliferation, apoptosis and autophagy of multiple myeloma cells]. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2018;26:817-23.
135. Hsu J, Shi Y, Krajewski S, et al. The AKT kinase is activated in multiple myeloma tumor cells. Blood 2001;98:2853-5.
136. Chen P, Wen X, Wang B, et al. PI3K/Akt inhibitor LY294002 potentiates homoharringtonine antimyeloma activity in myeloma cells adhered to stromal cells and in SCID mouse xenograft. Ann Hematol 2018;97:865-75.
137. Moriya S, Komatsu S, Yamasaki K, et al. Targeting the integrated networks of aggresome formation, proteasome, and autophagy potentiates ER stress-mediated cell death in multiple myeloma cells. Int J Oncol 2015;46:474-86.
138. Waldschmidt JM, Keller A, Ihorst G, et al. Safety and efficacy of vorinostat, bortezomib, doxorubicin and dexamethasone in a phase I/II study for relapsed or refractory multiple myeloma (VERUMM study: vorinostat in elderly, relapsed and unfit multiple myeloma). Haematologica 2018;103:e473-9.
139. Montanari F, Lu M, Marcus S, Saran A, Malankar A, Mazumder A. A phase II trial of chloroquine in combination with Bortezomib and Cyclophosphamide in patients with relapsed and refractory multiple myeloma. Blood 2014;124:5775.
140. Salimi A, Schroeder KM, Schemionek-Reinders M, et al. Targeting autophagy increases the efficacy of proteasome inhibitor treatment in multiple myeloma by induction of apoptosis and activation of JNK. BMC Cancer 2022;22:735.
141. McAfee Q, Zhang Z, Samanta A, et al. Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency. Proc Natl Acad Sci U S A 2012;109:8253-8.
142. Fatfat Z, Fatfat M, Gali-Muhtasib H. Therapeutic potential of thymoquinone in combination therapy against cancer and cancer stem cells. World J Clin Oncol 2021;12:522-43.
143. Günther A, Baumann P, Burger R, et al. Activity of everolimus (RAD001) in relapsed and/or refractory multiple myeloma: a phase I study. Haematologica 2015;100:541-7.
144. Liu H, Liu Y, Fu R, Shao Z. Everolimus shows synergistic anti-myeloma effects with bortezomib via the AKT/mTOR pathway. Blood 2017;130:5396.
145. Rizzieri DA, Feldman E, Dipersio JF, et al. A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res 2008;14:2756-62.
146. Ghobrial IM, Weller E, Vij R, et al. Weekly bortezomib in combination with temsirolimus in relapsed or relapsed and refractory multiple myeloma: a multicentre, phase 1/2, open-label, dose-escalation study. Lancet Oncol 2011;12:263-72.
147. Cirstea D, Santo L, Hideshima T, et al. Delineating the mTOR kinase pathway using a dual TORC1/2 inhibitor, AZD8055, in multiple myeloma. Mol Cancer Ther 2014;13:2489-500.
148. Peterson TR, Laplante M, Thoreen CC, et al. DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell 2009;137:873-86.
149. Lamanuzzi A, Saltarella I, Desantis V, et al. Inhibition of mTOR complex 2 restrains tumor angiogenesis in multiple myeloma. Oncotarget 2018;9:20563-77.
150. Richardson PG, Nagler A, Ben-Yehuda D, et al. Randomized, placebo-controlled, phase 3 study of perifosine combined with bortezomib and dexamethasone in patients with relapsed, refractory multiple myeloma previously treated with bortezomib. EJHaem 2020;1:94-102.
151. Dolly SO, Wagner AJ, Bendell JC, et al. Phase I study of apitolisib (GDC-0980), dual phosphatidylinositol-3-kinase and mammalian target of rapamycin kinase inhibitor, in patients with advanced solid tumors. Clin Cancer Res 2016;22:2874-84.
152. Sternke-Hoffmann R, Pauly T, Norrild RK, et al. Widespread amyloidogenicity potential of multiple myeloma patient-derived immunoglobulin light chains. BMC Biol 2023;21:21.
153. Savvidou I, Khong TT, Spencer A. The role of autophagy in multiple myeloma progression. Blood 2017;130:5355.
154. Kawaguchi T, Miyazawa K, Moriya S, et al. Combined treatment with bortezomib plus bafilomycin A1 enhances the cytocidal effect and induces endoplasmic reticulum stress in U266 myeloma cells: crosstalk among proteasome, autophagy-lysosome and ER stress. Int J Oncol 2011;38:643-54.
155. Liu J, Hamrouni A, Wolowiec D, et al. Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-γ and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway. Blood 2007;110:296-304.
156. Gazitt Y, Shaughnessy P, Rothenberg M. A phase II trial with gemcitabine and paclitaxel for the treatment of refractory and relapsed multiple myeloma patients. Oncol Rep 2006;16:877-84.
157. Veldhoen RA, Banman SL, Hemmerling DR, et al. The chemotherapeutic agent paclitaxel inhibits autophagy through two distinct mechanisms that regulate apoptosis. Oncogene 2013;32:736-46.
158. Vogl DT, Stadtmauer EA, Tan KS, et al. Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma. Autophagy 2014;10:1380-90.
159. Vogl DT, Raje N, Jagannath S, et al. Ricolinostat, the first selective histone deacetylase 6 inhibitor, in combination with Bortezomib and Dexamethasone for relapsed or refractory multiple myeloma. Clin Cancer Res 2017;23:3307-15.
160. Yee AJ, Bensinger WI, Supko JG, et al. Ricolinostat plus lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: a multicentre phase 1b trial. Lancet Oncol 2016;17:1569-78.
161. Yee AJ, Hari P, Marcheselli R, et al. Outcomes in patients with relapsed or refractory multiple myeloma in a phase I study of everolimus in combination with lenalidomide. Br J Haematol 2014;166:401-9.
162. Solomon VR, Lee H. Chloroquine and its analogs: a new promise of an old drug for effective and safe cancer therapies. Eur J Pharmacol 2009;625:220-33.
163. San-Miguel JF, Hungria VT, Yoon SS, et al. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol 2014;15:1195-206.
164. Li J, Liu R, Lei Y, et al. Proteomic analysis revealed association of aberrant ROS signaling with suberoylanilide hydroxamic acid-induced autophagy in Jurkat T-leukemia cells. Autophagy 2010;6:711-24.
165. Watanabe T, Nagase K, Chosa M, Tobinai K. Schwann cell autophagy induced by SAHA, 17-AAG, or clonazepam can reduce bortezomib-induced peripheral neuropathy. Br J Cancer 2010;103:1580-7.
166. Van Nuffel AM, Sukhatme V, Pantziarka P, Meheus L, Sukhatme VP, Bouche G. Repurposing drugs in oncology (ReDO)-clarithromycin as an anti-cancer agent. Ecancermedicalscience 2015;9:513.
167. Takemori N, Imai G, Hoshino K, Ooi A, Kojima M. A novel combination of bortezomib, lenalidomide, and clarithromycin produced stringent complete response in refractory multiple myeloma complicated with diabetes mellitus - clinical significance and possible mechanisms: a case report. J Med Case Rep 2018;12:40.
168. Ma Y, Jin Z, Yu K, Liu Q. NVP-BEZ235-induced autophagy as a potential therapeutic approach for multiple myeloma. Am J Transl Res 2019;11:87-105.
169. Leng H, Zhang H, Li L, et al. Modulating glycosphingolipid metabolism and autophagy improves outcomes in pre-clinical models of myeloma bone disease. Nat Commun 2022;13:7868.
170. Han Q, Bai H, Xu Y, et al. Solamargine induces autophagy-mediated apoptosis and enhances bortezomib activity in multiple myeloma. Clin Exp Pharmacol Physiol 2022;49:674-85.
171. Dykstra KM, Allen C, Born EJ, Tong H, Holstein SA. Mechanisms for autophagy modulation by isoprenoid biosynthetic pathway inhibitors in multiple myeloma cells. Oncotarget 2015;6:41535-49.
172. Wu X, Liu Y, Zhang E, et al. Dihydroartemisinin modulates apoptosis and autophagy in multiple myeloma through the P38/MAPK and Wnt/β-catenin signaling pathways. Oxid Med Cell Longev 2020;2020:6096391.
173. Palacios C, Martín-Pérez R, López-Pérez AI, Pandiella A, López-Rivas A. Autophagy inhibition sensitizes multiple myeloma cells to 17-dimethylaminoethylamino-17-demethoxygeldanamycin-induced apoptosis. Leuk Res 2010;34:1533-8.
174. Cao B, Li J, Zhou X, et al. Clioquinol induces pro-death autophagy in leukemia and myeloma cells by disrupting the mTOR signaling pathway. Sci Rep 2014;4:5749.
175. Li A, Chen X, Jing Z, Chen J. Trifluoperazine induces cellular apoptosis by inhibiting autophagy and targeting NUPR1 in multiple myeloma. FEBS Open Bio 2020;10:2097-106.
176. Zhou H, Luo W, Zeng C, et al. PP2A mediates apoptosis or autophagic cell death in multiple myeloma cell lines. Oncotarget 2017;8:80770-89.
177. Liao A, Hu R, Zhao Q, et al. Autophagy induced by FTY720 promotes apoptosis in U266 cells. Eur J Pharm Sci 2012;45:600-5.
178. Choi JR, Kozalak G, di Bari I, et al. In vitro human cancer models for biomedical applications. Cancers 2022;14:2284.
179. Mehta P, Rahman Z, Ten Dijke P, Boukany PE. Microfluidics meets 3D cancer cell migration. Trends Cancer 2022;8:683-97.