Cuproptosis Related Gene DLD Associated with Poor Prognosis and Malignant Biological Characteristics in Lung Adenocarcinoma

Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]

Siegel, R.L.; Miller, K.D.; Wagle, N.S.; Jemal, A. Cancer statistics, 2023. CA Cancer J. Clin., 2023, 73(1), 17-48.
[http://dx.doi.org/10.3322/caac.21763] [PMID: 36633525]

Barta, J.A.; Powell, C.A.; Wisnivesky, J.P. Global epidemiology of lung cancer. Ann. Glob. Health, 2019, 85(1), 8.
[http://dx.doi.org/10.5334/aogh.2419] [PMID: 30741509]

Ucvet, A.; Yazgan, S.; Gursoy, S.; Samancilar, O. Prognosis of resected non-small cell lung cancer with ipsilateral pulmonary metastasis. Thorac. Cardiovasc. Surg., 2020, 68(2), 176-182.
[http://dx.doi.org/10.1055/s-0038-1667169] [PMID: 30060270]

Martínez-Reyes, I.; Chandel, N.S. Cancer metabolism: Looking forward. Nat. Rev. Cancer, 2021, 21(10), 669-680.
[http://dx.doi.org/10.1038/s41568-021-00378-6] [PMID: 34272515]

Pavlova, N.N.; Zhu, J.; Thompson, C.B. The hallmarks of cancer metabolism: Still emerging. Cell Metab., 2022, 34(3), 355-377.
[http://dx.doi.org/10.1016/j.cmet.2022.01.007] [PMID: 35123658]

Rodrigues Mantuano, N.; Natoli, M.; Zippelius, A.; Läubli, H. Tumor-associated carbohydrates and immunomodulatory lectins as targets for cancer immunotherapy. J. Immunother. Cancer, 2020, 8(2), e001222.
[http://dx.doi.org/10.1136/jitc-2020-001222] [PMID: 33020245]

Sivanand, S.; Vander Heiden, M.G. Emerging roles for branched-chain amino acid metabolism in cancer. Cancer Cell, 2020, 37(2), 147-156.
[http://dx.doi.org/10.1016/j.ccell.2019.12.011] [PMID: 32049045]

Mou, Y.; Wang, J.; Wu, J.; He, D.; Zhang, C.; Duan, C.; Li, B. Ferroptosis, a new form of cell death: Opportunities and challenges in cancer. J. Hematol. Oncol., 2019, 12(1), 34.
[http://dx.doi.org/10.1186/s13045-019-0720-y] [PMID: 30925886]

Moujalled, D.; Strasser, A.; Liddell, J.R. Molecular mechanisms of cell death in neurological diseases. Cell Death Differ., 2021, 28(7), 2029-2044.
[http://dx.doi.org/10.1038/s41418-021-00814-y] [PMID: 34099897]

Chen, J.; Jiang, Y.; Shi, H.; Peng, Y.; Fan, X.; Li, C. The molecular mechanisms of copper metabolism and its roles in human diseases. Pflugers Arch., 2020, 472(10), 1415-1429.
[http://dx.doi.org/10.1007/s00424-020-02412-2] [PMID: 32506322]

Ruiz, L.M.; Libedinsky, A.; Elorza, A.A. Role of copper on mitochondrial function and metabolism. Front. Mol. Biosci., 2021, 8, 711227.
[http://dx.doi.org/10.3389/fmolb.2021.711227] [PMID: 34504870]

Nanni, V.; Di Marco, G.; Sacchetti, G.; Canini, A.; Gismondi, A. Oregano phytocomplex induces programmed cell death in melanoma lines via mitochondria and DNA damage. Foods, 2020, 9(10), 1486.
[http://dx.doi.org/10.3390/foods9101486] [PMID: 33080917]

Li, Y. Copper homeostasis: Emerging target for cancer treatment. IUBMB Life, 2020, 72(9), 1900-1908.
[http://dx.doi.org/10.1002/iub.2341] [PMID: 32599675]

Michniewicz, F.; Saletta, F.; Rouaen, J.R.C.; Hewavisenti, R.V.; Mercatelli, D.; Cirillo, G.; Giorgi, F.M.; Trahair, T.; Ziegler, D.; Vittorio, O. Copper: An intracellular Achilles’ heel allowing the targeting of epigenetics, kinase pathways, and cell metabolism in cancer therapeutics. ChemMedChem, 2021, 16(15), 2315-2329.
[http://dx.doi.org/10.1002/cmdc.202100172] [PMID: 33890721]

Aubert, L.; Nandagopal, N.; Steinhart, Z.; Lavoie, G.; Nourreddine, S.; Berman, J.; Saba-El-Leil, M.K.; Papadopoli, D.; Lin, S.; Hart, T.; Macleod, G.; Topisirovic, I.; Gaboury, L.; Fahrni, C.J.; Schramek, D.; Meloche, S.; Angers, S.; Roux, P.P. Copper bioavailability is a KRAS-specific vulnerability in colorectal cancer. Nat. Commun., 2020, 11(1), 3701.
[http://dx.doi.org/10.1038/s41467-020-17549-y] [PMID: 32709883]

Chen, F.; Wang, J.; Chen, J.; Yan, L.; Hu, Z.; Wu, J.; Bao, X.; Lin, L.; Wang, R.; Cai, L.; Lin, L.; Qiu, Y.; Liu, F.; He, B. Serum copper and zinc levels and the risk of oral cancer: A new insight based on large-scale case–control study. Oral Dis., 2019, 25(1), 80-86.
[http://dx.doi.org/10.1111/odi.12957] [PMID: 30107072]

Arnesano, F.; Natile, G. Interference between copper transport systems and platinum drugs. Semin. Cancer Biol., 2021, 76, 173-188.
[http://dx.doi.org/10.1016/j.semcancer.2021.05.023] [PMID: 34058339]

Tsvetkov, P.; Coy, S.; Petrova, B.; Dreishpoon, M.; Verma, A.; Abdusamad, M.; Rossen, J.; Joesch-Cohen, L.; Humeidi, R.; Spangler, R.D.; Eaton, J.K.; Frenkel, E.; Kocak, M.; Corsello, S.M.; Lutsenko, S.; Kanarek, N.; Santagata, S.; Golub, T.R. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science, 2022, 375(6586), 1254-1261.
[http://dx.doi.org/10.1126/science.abf0529] [PMID: 35298263]

Lu, Y.; Luo, X.; Wang, Q.; Chen, J.; Zhang, X.; Li, Y.; Chen, Y.; Li, X.; Han, S. A novel necroptosis-related lncRNA signature predicts the prognosis of lung adenocarcinoma. Front. Genet., 2022, 13, 862741.
[http://dx.doi.org/10.3389/fgene.2022.862741] [PMID: 35368663]

Lin, W.; Chen, Y.; Wu, B.; chen, Y.; Li, Z. Identification of the pyroptosis-related prognostic gene signature and the associated regulation axis in lung adenocarcinoma. Cell Death Discov., 2021, 7(1), 161.
[http://dx.doi.org/10.1038/s41420-021-00557-2] [PMID: 34226539]

Peng, X.; Wu, H.; Zhang, B.; Xu, C.; Lang, J. A novel nucleic acid sensing-related genes signature for predicting immunotherapy efficacy and prognosis of lung adenocarcinoma. Curr. Cancer Drug Targets, 2023.
[PMID: 37592781]

Goldman, M.J.; Craft, B.; Hastie, M.; Repečka, K.; McDade, F.; Kamath, A.; Banerjee, A.; Luo, Y.; Rogers, D.; Brooks, A.N.; Zhu, J.; Haussler, D. Visualizing and interpreting cancer genomics data via the Xena platform. Nat. Biotechnol., 2020, 38(6), 675-678.
[http://dx.doi.org/10.1038/s41587-020-0546-8] [PMID: 32444850]

Karlstaedt, A.; Barrett, M.; Hu, R.; Gammons, S.T.; Ky, B. Cardio-oncology. JACC Basic Transl. Sci., 2021, 6(8), 705-718.
[http://dx.doi.org/10.1016/j.jacbts.2021.05.008] [PMID: 34466757]

Qin, Y.; Liu, Y.; Xiang, X.; Long, X.; Chen, Z.; Huang, X.; Yang, J.; Li, W. Cuproptosis correlates with immunosuppressive tumor microenvironment based on pan-cancer multiomics and single-cell sequencing analysis. Mol. Cancer, 2023, 22(1), 59.
[http://dx.doi.org/10.1186/s12943-023-01752-8] [PMID: 36959665]

da Silva, D.A.; De Luca, A.; Squitti, R.; Rongioletti, M.; Rossi, L.; Machado, C.M.L.; Cerchiaro, G. Copper in tumors and the use of copper-based compounds in cancer treatment. J. Inorg. Biochem., 2022, 226, 111634.
[http://dx.doi.org/10.1016/j.jinorgbio.2021.111634] [PMID: 34740035]

Ge, E.J.; Bush, A.I.; Casini, A.; Cobine, P.A.; Cross, J.R.; DeNicola, G.M.; Dou, Q.P.; Franz, K.J.; Gohil, V.M.; Gupta, S.; Kaler, S.G.; Lutsenko, S.; Mittal, V.; Petris, M.J.; Polishchuk, R.; Ralle, M.; Schilsky, M.L.; Tonks, N.K.; Vahdat, L.T.; Van Aelst, L.; Xi, D.; Yuan, P.; Brady, D.C.; Chang, C.J.; Xi, D.; Yuan, P. Connecting copper and cancer: From transition metal signalling to metalloplasia. Nat. Rev. Cancer, 2022, 22(2), 102-113.
[http://dx.doi.org/10.1038/s41568-021-00417-2] [PMID: 34764459]

Luo, J.; Wang, H.; Wang, L.; Wang, G.; Yao, Y.; Xie, K.; Li, X.; Xu, L.; Shen, Y.; Ren, B. lncRNA GAS6-AS1 inhibits progression and glucose metabolism reprogramming in LUAD via repressing E2F1-mediated transcription of GLUT1. Mol. Ther. Nucleic Acids, 2021, 25, 11-24.
[http://dx.doi.org/10.1016/j.omtn.2021.04.022] [PMID: 34141461]

Strasser, A.; Vaux, D.L. Cell death in the origin and treatment of cancer. Mol. Cell, 2020, 78(6), 1045-1054.
[http://dx.doi.org/10.1016/j.molcel.2020.05.014] [PMID: 32516599]

Kahlson, M.A.; Dixon, S.J. Copper-induced cell death. Science, 2022, 375(6586), 1231-1232.
[http://dx.doi.org/10.1126/science.abo3959] [PMID: 35298241]

Babak, M.V.; Ahn, D. Modulation of intracellular copper levels as the mechanism of action of anticancer copper complexes: Clinical relevance. Biomedicines, 2021, 9(8), 852.
[http://dx.doi.org/10.3390/biomedicines9080852] [PMID: 34440056]

Theodosis-Nobelos, P.; Papagiouvannis, G.; Tziona, P.; Rekka, E.A. Lipoic acid. Kinetics and pluripotent biological properties and derivatives. Mol. Biol. Rep., 2021, 48(9), 6539-6550.
[http://dx.doi.org/10.1007/s11033-021-06643-z] [PMID: 34420148]

Cronan, J.E. Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes. Front. Genet., 2020, 11, 510.
[http://dx.doi.org/10.3389/fgene.2020.00510] [PMID: 32508887]

Fleminger, G.; Dayan, A. The moonlighting activities of dihydrolipoamide dehydrogenase: Biotechnological and biomedical applications. J. Mol. Recognit., 2021, 34(11), e2924.
[http://dx.doi.org/10.1002/jmr.2924] [PMID: 34164859]

Solmonson, A.; DeBerardinis, R.J. Lipoic acid metabolism and mitochondrial redox regulation. J. Biol. Chem., 2018, 293(20), 7522-7530.
[http://dx.doi.org/10.1074/jbc.TM117.000259] [PMID: 29191830]

Dayan, A.; Yeheskel, A.; Lamed, R.; Fleminger, G.; Ashur-Fabian, O. Dihydrolipoamide dehydrogenase moonlighting activity as a DNA chelating agent. Proteins, 2020.
[PMID: 32761961]

Yumnam, S.; Kang, M.C.; Oh, S.H.; Kwon, H.C.; Kim, J.C.; Jung, E.S.; Lee, C.H.; Lee, A.Y.; Hwang, J.I.; Kim, S.Y. Downregulation of dihydrolipoyl dehydrogenase by UVA suppresses melanoma progression via triggering oxidative stress and altering energy metabolism. Free Radic. Biol. Med., 2021, 162, 77-87.
[http://dx.doi.org/10.1016/j.freeradbiomed.2020.11.037] [PMID: 33279616]

Stowe, R.C.; Sun, Q.; Elsea, S.H.; Scaglia, F. LIPT1 deficiency presenting as early infantile epileptic encephalopathy, Leigh disease, and secondary pyruvate dehydrogenase complex deficiency. Am. J. Med. Genet. A., 2018, 176(5), 1184-1189.
[http://dx.doi.org/10.1002/ajmg.a.38654] [PMID: 29681092]

Ni, M.; Solmonson, A.; Pan, C.; Yang, C.; Li, D.; Notzon, A.; Cai, L.; Guevara, G.; Zacharias, L.G.; Faubert, B.; Vu, H.S.; Jiang, L.; Ko, B.; Morales, N.M.; Pei, J.; Vale, G.; Rakheja, D.; Grishin, N.V.; McDonald, J.G.; Gotway, G.K.; McNutt, M.C.; Pascual, J.M.; DeBerardinis, R.J. Functional assessment of Lipoyltransferase-1 deficiency in cells, mice, and humans. Cell Rep., 2019, 27(5), 1376-1386.e6.
[http://dx.doi.org/10.1016/j.celrep.2019.04.005] [PMID: 31042466]

Solmonson, A.; Faubert, B.; Gu, W.; Rao, A.; Cowdin, M.A.; Menendez-Montes, I.; Kelekar, S.; Rogers, T.J.; Pan, C.; Guevara, G.; Tarangelo, A.; Zacharias, L.G.; Martin-Sandoval, M.S.; Do, D.; Pachnis, P.; Dumesnil, D.; Mathews, T.P.; Tasdogan, A.; Pham, A.; Cai, L.; Zhao, Z.; Ni, M.; Cleaver, O.; Sadek, H.A.; Morrison, S.J.; DeBerardinis, R.J. Compartmentalized metabolism supports midgestation mammalian development. Nature, 2022, 604(7905), 349-353.
[http://dx.doi.org/10.1038/s41586-022-04557-9] [PMID: 35388219]

Li, J.; Tuo, D.; Guo, G.; Gan, J. Aberrant expression of cuproptosis-related gene LIPT1 is associated with metabolic dysregulation of fatty acid and prognosis in hepatocellular carcinoma. J. Cancer Res. Clin. Oncol., 2023, 149(17), 15763-15779.
[http://dx.doi.org/10.1007/s00432-023-05325-6] [PMID: 37668796]

Yan, C.; Niu, Y.; Ma, L.; Tian, L.; Ma, J. System analysis based on the cuproptosis-related genes identifies LIPT1 as a novel therapy target for liver hepatocellular carcinoma. J. Transl. Med., 2022, 20(1), 452.
[http://dx.doi.org/10.1186/s12967-022-03630-1] [PMID: 36195876]

Najafi, N.; Mehri, S.; Ghasemzadeh Rahbardar, M.; Hosseinzadeh, H. Effects of alpha lipoic acid on metabolic syndrome: A comprehensive review. Phytother. Res., 2022, 36(6), 2300-2323.
[http://dx.doi.org/10.1002/ptr.7406] [PMID: 35234312]

Tanaka, A.; Sakaguchi, S. Targeting Treg cells in cancer immunotherapy. Eur. J. Immunol., 2019, 49(8), 1140-1146.
[http://dx.doi.org/10.1002/eji.201847659] [PMID: 31257581]

Peng, X.; Zheng, J.; Liu, T.; Zhou, Z.; Song, C.; Geng, Y.; Wang, Z.; Huang, Y. Tumor microenvironment heterogeneity, potential therapeutic avenues, and emerging therapies. Curr. Cancer Drug Targets, 2023.
[PMID: 37537777]

DeNardo, D.G.; Ruffell, B. Macrophages as regulators of tumour immunity and immunotherapy. Nat. Rev. Immunol., 2019, 19(6), 369-382.
[http://dx.doi.org/10.1038/s41577-019-0127-6] [PMID: 30718830]

Obarorakpor, N.; Patel, D.; Boyarov, R.; Amarsaikhan, N.; Cepeda, J.R.; Eastes, D.; Robertson, S.; Johnson, T.; Yang, K.; Tang, Q.; Zhang, L. Regulatory T cells targeting a pathogenic MHC class II: Insulin peptide epitope postpone spontaneous autoimmune diabetes. Front. Immunol., 2023, 14, 1207108.
[http://dx.doi.org/10.3389/fimmu.2023.1207108] [PMID: 37593744]

Marhelava, K.; Krawczyk, M.; Firczuk, M.; Fidyt, K. CAR-T cells shoot for new targets: Novel approaches to boost adoptive cell therapy for b cell-derived malignancies. Cells, 2022, 11(11), 1804.
[http://dx.doi.org/10.3390/cells11111804] [PMID: 35681499]

Akkaya, B.; Shevach, E.M. Regulatory T cells: Master thieves of the immune system. Cell. Immunol., 2020, 355, 104160.
[http://dx.doi.org/10.1016/j.cellimm.2020.104160] [PMID: 32711171]

Chen, Z.; Yang, X.; Bi, G.; Liang, J.; Hu, Z.; Zhao, M.; Li, M.; Lu, T.; Zheng, Y.; Sui, Q.; Yang, Y.; Zhan, C.; Jiang, W.; Wang, Q.; Tan, L. Ligand-receptor interaction atlas within and between tumor cells and T cells in lung adenocarcinoma. Int. J. Biol. Sci., 2020, 16(12), 2205-2219.
[http://dx.doi.org/10.7150/ijbs.42080] [PMID: 32549766]

Lim, S.A.; Wei, J.; Nguyen, T.L.M.; Shi, H.; Su, W.; Palacios, G.; Dhungana, Y.; Chapman, N.M.; Long, L.; Saravia, J.; Vogel, P.; Chi, H. Lipid signalling enforces functional specialization of T_reg cells in tumours. Nature, 2021, 591(7849), 306-311.
[http://dx.doi.org/10.1038/s41586-021-03235-6] [PMID: 33627871]

Shimasaki, N.; Jain, A.; Campana, D. NK cells for cancer immunotherapy. Nat. Rev. Drug Discov., 2020, 19(3), 200-218.
[http://dx.doi.org/10.1038/s41573-019-0052-1] [PMID: 31907401]

Wu, S.Y.; Fu, T.; Jiang, Y.Z.; Shao, Z.M. Natural killer cells in cancer biology and therapy. Mol. Cancer, 2020, 19(1), 120.
[http://dx.doi.org/10.1186/s12943-020-01238-x] [PMID: 32762681]

Zhu, Z.; Zhang, H.; Chen, B.; Liu, X.; Zhang, S.; Zong, Z.; Gao, M. PD-L1-mediated immunosuppression in glioblastoma is associated with the infiltration and M2-polarization of tumor-associated macrophages. Front. Immunol., 2020, 11, 588552.
[http://dx.doi.org/10.3389/fimmu.2020.588552] [PMID: 33329573]

Belgiovine, C.; Digifico, E.; Anfray, C.; Ummarino, A.; Torres Andón, F. Targeting tumor-associated macrophages in anti-cancer therapies: Convincing the traitors to do the right thing. J. Clin. Med., 2020, 9(10), 3226.
[http://dx.doi.org/10.3390/jcm9103226] [PMID: 33050070]

Borghaei, H.; Gettinger, S.; Vokes, E.E.; Chow, L.Q.M.; Burgio, M.A.; de Castro Carpeno, J.; Pluzanski, A.; Arrieta, O.; Frontera, O.A.; Chiari, R.; Butts, C.; Wójcik-Tomaszewska, J.; Coudert, B.; Garassino, M.C.; Ready, N.; Felip, E.; García, M.A.; Waterhouse, D.; Domine, M.; Barlesi, F.; Antonia, S.; Wohlleber, M.; Gerber, D.E.; Czyzewicz, G.; Spigel, D.R.; Crino, L.; Eberhardt, W.E.E.; Li, A.; Marimuthu, S.; Brahmer, J.; García, M.A.; Waterhouse, D.; Pluzanski, A.; Arrieta, O.; Vokes, E.E. Five-year outcomes from the randomized, phase III trials checkmate 017 and 057: Nivolumab versus docetaxel in previously treated non–small-cell lung cancer. J. Clin. Oncol., 2021, 39(7), 723-733.
[http://dx.doi.org/10.1200/JCO.20.01605] [PMID: 33449799]

Mok, T.S.K.; Wu, Y.L.; Kudaba, I.; Kowalski, D.M.; Cho, B.C.; Turna, H.Z.; Castro, G., Jr; Srimuninnimit, V.; Laktionov, K.K.; Bondarenko, I.; Kubota, K.; Lubiniecki, G.M.; Zhang, J.; Kush, D.; Lopes, G.; Adamchuk, G.; Ahn, M-J.; Alexandru, A.; Altundag, O.; Alyasova, A.; Andrusenko, O.; Aoe, K.; Araujo, A.; Aren, O.; Arrieta Rodriguez, O.; Ativitavas, T.; Avendano, O.; Barata, F.; Barrios, C.H.; Beato, C.; Bergstrom, P.; Betticher, D.; Bolotina, L.; Bondarenko, I.; Botha, M.; Buddu, S.; Caglevic, C.; Cardona, A.; Castro, G., Jr; Castro, H.; Cay Senler, F.; Cerny, C.A.S.; Cesas, A.; Chan, G-C.; Chang, J.; Chen, G.; Chen, X.; Cheng, S.; Cheng, Y.; Cherciu, N.; Chiu, C-H.; Cho, B.C.; Cicenas, S.; Ciurescu, D.; Cohen, G.; Costa, M.A.; Danchaivijitr, P.; De Angelis, F.; de Azevedo, S.J.; Dediu, M.; Deliverski, T.; De Marchi, P.R.M.; de The Bustamante Valles, F.; Ding, Z.; Doganov, B.; Dreosti, L.; Duarte, R.; Edusma-Dy, R.; Emelyanov, S.; Erman, M.; Fan, Y.; Fein, L.; Feng, J.; Fenton, D.; Fernandes, G.; Ferreira, C.; Franke, F.A.; Freitas, H.; Fujisaka, Y.; Galindo, H.; Galvez, C.; Ganea, D.; Gil, N.; Girotto, G.; Goker, E.; Goksel, T.; Gomez Aubin, G.; Gomez Wolff, L.; Griph, H.; Gumus, M.; Hall, J.; Hart, G.; Havel, L.; He, J.; He, Y.; Hernandez Hernandez, C.; Hespanhol, V.; Hirashima, T.; Ho, C.M.J.; Horiike, A.; Hosomi, Y.; Hotta, K.; Hou, M.; How, S.H.; Hsia, T-C.; Hu, Y.; Ichiki, M.; Imamura, F.; Ivashchuk, O.; Iwamoto, Y.; Jaal, J.; Jassem, J.; Jordaan, C.; Juergens, R.A.; Kaen, D.; Kalinka-Warzocha, E.; Karaseva, N.; Karaszewska, B.; Kazarnowicz, A.; Kasahara, K.; Katakami, N.; Kato, T.; Kawaguchi, T.; Kim, J.H.; Kishi, K.; Kolek, V.; Koleva, M.; Kolman, P.; Koubkova, L.; Kowalyszyn, R.; Kowalski, D.; Koynov, K.; Ksienski, D.; Kubota, K.; Kudaba, I.; Kurata, T.; Kuusk, G.; Kuzina, L.; Laczo, I.; Ladrera, G.E.I.; Laktionov, K.; Landers, G.; Lazarev, S.; Lerzo, G.; Lesniewski Kmak, K.; Li, W.; Liam, C.K.; Lifirenko, I.; Lipatov, O.; Liu, X.; Liu, Z.; Lo, S.H.; Lopes, V.; Lopez, K.; Lu, S.; Martinengo, G.; Mas, L.; Matrosova, M.; Micheva, R.; Milanova, Z.; Miron, L.; Mok, T.; Molina, M.; Murakami, S.; Nakahara, Y.; Nguyen, T.Q.; Nishimura, T.; Ochsenbein, A.; Ohira, T.; Ohman, R.; Ong, C.K.; Ostoros, G.; Ouyang, X.; Ovchinnikova, E.; Ozyilkan, O.; Petruzelka, L.; Pham, X.D.; Picon, P.; Piko, B.; Poltoratsky, A.; Ponomarova, O.; Popelkova, P.; Purkalne, G.; Qin, S.; Ramlau, R.; Rappaport, B.; Rey, F.; Richardet, E.; Roubec, J.; Ruff, P.; Rusyn, A.; Saka, H.; Salas, J.; Sandoval, M.; Santos, L.; Sawa, T.; Seetalarom, K.; Seker, M.; Seki, N.; Seolwane, F.; Shepherd, L.; Shevnya, S.; Shimada, A.K.; Shparyk, Y.; Sinielnikov, I.; Sirbu, D.; Smaletz, O.; Soares, J.P.H.; Sookprasert, A.; Speranza, G.; Srimuninnimit, V.; Sriuranpong, V.; Stara, Z.; Su, W-C.; Sugawara, S.; Szpak, W.; Takahashi, K.; Takigawa, N.; Tanaka, H.; Tan Chun Bing, J.; Tang, Q.; Taranov, P.; Tejada, H.; Tho, L.M.; Torii, Y.; Trukhyn, D.; Turdean, M.; Turna, H.; Ursol, G.; Vanasek, J.; Varela, M.; Vallejo, M.; Vera, L.; Victorino, A-P.; Vlasek, T.; Vynnychenko, I.; Wang, B.; Wang, J.; Wang, K.; Wu, Y.; Yamada, K.; Yang, C-H.; Yokoyama, T.; Yokoyama, T.; Yoshioka, H.; Yumuk, F.; Zambrano, A.; Zarba, J.J.; Zarubenkov, O.; Zemaitis, M.; Zhang, L.; Zhang, L.; Zhang, X.; Zhao, J.; Zhou, C.; Zhou, J.; Zhou, Q.; Zippelius, A. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): A randomised, open-label, controlled, phase 3 trial. Lancet, 2019, 393(10183), 1819-1830.
[http://dx.doi.org/10.1016/S0140-6736(18)32409-7] [PMID: 30955977]

Garassino, M.C.; Gadgeel, S.; Speranza, G.; Felip, E.; Esteban, E.; Dómine, M.; Hochmair, M.J.; Powell, S.F.; Bischoff, H.G.; Peled, N.; Grossi, F.; Jennens, R.R.; Reck, M.; Hui, R.; Garon, E.B.; Kurata, T.; Gray, J.E.; Schwarzenberger, P.; Jensen, E.; Pietanza, M.C.; Rodríguez-Abreu, D. Pembrolizumab plus pemetrexed and platinum in nonsquamous non–small-cell lung cancer: 5-year outcomes from the phase 3 KEYNOTE-189 study. J. Clin. Oncol., 2023, 41(11), 1992-1998.
[http://dx.doi.org/10.1200/JCO.22.01989] [PMID: 36809080]

Brahmer, J.R.; Lee, J.S.; Ciuleanu, T.E.; Bernabe Caro, R.; Nishio, M.; Urban, L.; Audigier-Valette, C.; Lupinacci, L.; Sangha, R.; Pluzanski, A.; Burgers, J.; Mahave, M.; Ahmed, S.; Schoenfeld, A.J.; Paz-Ares, L.G.; Reck, M.; Borghaei, H.; O’Byrne, K.J.; Gupta, R.G.; Bushong, J.; Li, L.; Blum, S.I.; Eccles, L.J.; Ramalingam, S.S. Five-year survival outcomes with nivolumab plus ipilimumab versus chemotherapy as first-line treatment for metastatic non–small-cell lung cancer in CheckMate 227. J. Clin. Oncol., 2023, 41(6), 1200-1212.
[http://dx.doi.org/10.1200/JCO.22.01503] [PMID: 36223558]

Wang, W.; Bai, L.; Xu, D.; Li, W.; Cui, J. Immunotherapy: A potential approach to targeting cancer stem cells. Curr. Cancer Drug Targets, 2021, 21(2), 117-131.
[http://dx.doi.org/10.2174/1568009620666200504111914] [PMID: 32364076]