L-asparaginase-mediated Therapy in L-asparagine Auxotrophic Cancers: A Review

Burney, I.A.; Al-Moundhri, M.S. Major advances in the treatment of cancer: What does a non-oncologist need to know? Sultan Qaboos Univ. Med. J., 2008, 8(2), 137-148.
[PMID: 21748051]

Deonarain, M.P.; Epenetos, A.A. Targeting enzymes for cancer therapy: Old enzymes in new roles. Br. J. Cancer, 1994, 70(5), 786-794.
[http://dx.doi.org/10.1038/bjc.1994.400] [PMID: 7947082]

Maggi, M.; Scotti, C. Enzymes in metabolic anticancer therapy. In: Therapeutic Enzymes: Function and Clinical Implications; Labrou, N., Ed.; Springer: Singapore, 2019, Vol. 1148, pp. 173-199.
[http://dx.doi.org/10.1007/978-981-13-7709-9_9]

Vellard, M. The enzyme as drug: Application of enzymes as pharmaceuticals. Curr. Opin. Biotechnol., 2003, 14(4), 444-450.
[http://dx.doi.org/10.1016/S0958-1669(03)00092-2] [PMID: 12943856]

Egler, R.A.; Ahuja, S.P.; Matloub, Y. L-asparaginase in the treatment of patients with acute lymphoblastic leukemia. J. Pharmacol. Pharmacother., 2016, 7(2), 62-71.
[http://dx.doi.org/10.4103/0976-500X.184769] [PMID: 27440950]

Hansen, H.H.; Canellos, G.P. L-asparaginase treatment of acute myeloblastic leukemia. Oncology, 1970, 24(5), 349-357.
[http://dx.doi.org/10.1159/000224536] [PMID: 5275037]

Horowitz, B.; Madras, B.K.; Meister, A.; Old, L.J.; Boyes, E.A.; Stockert, E. Asparagine synthetase activity of mouse leukemias. Science, 1968, 160(3827), 533-535.
[http://dx.doi.org/10.1126/science.160.3827.533] [PMID: 5689413]

Prager, M.D.; Bachynsky, N. Asparagine synthetase in asparaginase resistant and susceptible mouse lymphomas. Biochem. Biophys. Res. Commun., 1968, 31(1), 43-47.
[http://dx.doi.org/10.1016/0006-291X(68)90028-4] [PMID: 4869945]

Narta, U.K.; Kanwar, S.S.; Azmi, W. Pharmacological and clinical evaluation of L-asparaginase in the treatment of leukemia. Crit. Rev. Oncol. Hematol., 2007, 61(3), 208-221.
[http://dx.doi.org/10.1016/j.critrevonc.2006.07.009] [PMID: 17011787]

Broome, J.D. Evidence that the L-asparaginase activity of guinea pig serum is responsible for its antilymphoma effects. Nature, 1961, 191, 1114-1115.
[http://dx.doi.org/10.1038/1911114a0]

Broome, J.D. Evidence that the L-asparaginase of guinea pig serum is responsible for its antilymphoma effects. I. properties of the L-asparaginase of guinea pig serum in relation to those of the antilymphoma substance. J. Exp. Med., 1963, 118(1), 99-120.
[http://dx.doi.org/10.1084/jem.118.1.99] [PMID: 14015821]

Broome, J.D. Studies on the mechanism of tumor inhibition by L-asparaginase. Effects of the enzyme on asparagine levels in the blood, normal tissues, and 6C3HED lymphomas of mice: Differences in asparagine formation and utilization in asparaginase-sensitive and -resistant lymphoma cells. J. Exp. Med., 1968, 127(6), 1055-1072.
[http://dx.doi.org/10.1084/jem.127.6.1055] [PMID: 4871211]

Neuman, R.E.; McCoy, T.A. Dual requirement of Walker carcinosarcoma 256 in vitro for asparagine and glutamine. Science, 1956, 124(3212), 124-125.
[http://dx.doi.org/10.1126/science.124.3212.124] [PMID: 13337363]

Haley, E.E.; Fischer, G.A.; Welch, A.D. The requirement for L-asparagine of mouse leukemia cells L5178Y in culture. Cancer Res., 1961, 21, 532-536.
[PMID: 13710714]

Boyse, E.A.; Old, L.J.; Campbell, H.A.; Mashburn, L.T. Suppression of murine leukemias by L-asparaginase. Incidence of sensitivity among leukemias of various types: Comparative inhibitory activities of guinea pig serum L-asparaginase and Escherichia coli L-asparaginase. J. Exp. Med., 1967, 125(1), 17-31.
[http://dx.doi.org/10.1084/jem.125.1.17] [PMID: 5334543]

Pagliardi, G.L.; Gabutti, V.; Gavosto, F. Mechanism of action of L-asparaginase on the cell cycle and growth in acute lymphoblastic leukemia. Acta Haematol., 1973, 50(5), 257-268.
[http://dx.doi.org/10.1159/000208358] [PMID: 4202629]

Chand, S.; Mahajan, R.V.; Prasad, J.P.; Sahoo, D.K.; Mihooliya, K.N.; Dhar, M.S.; Sharma, G. A comprehensive review on microbial L-asparaginase: Bioprocessing, characterization, and industrial applications. Biotechnol. Appl. Biochem., 2020, 67(4), 619-647.
[http://dx.doi.org/10.1002/bab.1888]

Castro, D.; Marques, A.S.C.; Almeida, M.R.; de Paiva, G.B.; Bento, H.B.S.; Pedrolli, D.B.; Freire, M.G.; Tavares, A.P.M.; Santos-Ebinuma, V.C. L-asparaginase production review: Bioprocess design and biochemical characteristics. Appl. Microbiol. Biotechnol., 2021, 105(11), 4515-4534.
[http://dx.doi.org/10.1007/s00253-021-11359-y]

Rytting, M. Role of L-asparaginase in acute lymphoblastic leukemia: Focus on adult patients. Blood Lymphat. Cancer, 2012, 2, 117-124.
[http://dx.doi.org/10.2147/BLCTT.S18699]

Larson, R.A.; Dodge, R.K.; Burns, C.P.; Lee, E.J.; Stone, R.M.; Schulman, P.; Duggan, D.; Davey, F.R.; Sobol, R.E.; Frankel, S.R. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: Cancer and leukemia group B study 8811. Blood, 1995, 85(8), 2025-2037.
[http://dx.doi.org/10.1182/blood.V85.8.2025.bloodjournal8582025] [PMID: 7718875]

Block, K.I.; Gyllenhaal, C.; Lowe, L.; Amedei, A.; Amin, A.R.M.R.; Aquilano, K.; Arbiser, J.; Arreola, A.; Arzumanyan, A.; Ashraf, S.S.; Azmi, A.S.; Benencia, F.; Bhak-ta, D.; Bilsland, A.; Bishayee, A.; Blain, S.W.; Block, P.B.; Boosani, C.S.; Carey, T.E.; Carnero, A.; Carotenuto, M.; Casey, S.C.; Chakrabarti, M.; Chaturvedi, R.; Chen, G.Z.; Chen, H.; Chen, S.; Chen, Y.C.; Choi, B.K.; Ciriolo, M.R.; Coley, H.M.; Collins, A.R.; Connell, M.; Crawford, S.; Curran, C.S.; Dabrosin, C.; Damia, G.; Dasgupta, S.; DeBerardinis, R.J.; Decker, W.K.; Dhawan, P.; Diehl, A.M.E.; Dong, J-T.; Dou, Q.P.; Drew, J.E.; Elkord, E.; El-Rayes, B.; Feitelson, M.A.; Felsher, D.W.; Ferguso, L.R.; Fimognari, C.; Firestone, C.L.; Frezza, C.; Fujii, H.; Fuster, M.M.; Generali, D.; Georgakilas, A.G.; Gieseler, F.; Gilbertson, M.; Green, M.F.; Grue, B.; Guha, G.; Halicka, D.; Helferich, W.G.; Heneberg, P.; Hentosh, P.; Hirschey, M.D.; Hofseth, L.J.; Holcombe, R.F.; Honoki, K.; Hsu, H-Y.; Huang, G.S.; Jensen, L.D.; Jiang, W.G.; Jones, L.W.; Karpowicz, P.A.; Keith, W.N.; Kerkar, S.P.; Khan, G.N.; Khatami, M.; Ko, Y.H.; Kucuk, O.; Kulathinal, R.J.; Kumar, N.B.; Kwon, B.S.; Le, A.; Lea, M.A.; Lee, H-Y.; Lichtor, T.; Lin, L-T.; Locasale, J.W.; Lokeshwar, B.L.; Longo, V.D.; Lyssiotis, C.A.; MacKenzie, K.L.; Malhotra, M.; Marino, M.; Martinez-Chantar, M.L.; Matheu, A.; Maxwell, C.; McDonnell, E.; Meeker, A.K.; Mehrmohamadi, M.; Mehta, K.; Michelotti, G.A.; Mohammad, R.M.; Mohammed, S.I.; Morre, D.J.; Muralidhar, V.; Muqbil, I.; Murphy, M.P.; Nagaraju, G.P.; Nahta, R.; Niccolai, E.; Nowsheen, S.; Panis, C.; Pantano, F.; Parslow, V.R.; Pawelec, G.; Pedersen, P.L.; Poore, B.; Poudyal, D.; Prakash, S.; Prince, M.; Raffaghello, L.; Rathmell, J.C.; Rathmell, W.K.; Ray, S.K.; Reichrath, J.; Rezazadeh, S.; Ribatti, D.; Ricciardiello, L.; Robey, R.B.; Rodier, F.; Ru-pasinghe, H.P.V.; Russo, G.L.; Ryan, E.P.; Samadi, A.K.; Sanchez-Garcia, I.; Sanders, A.J.; Santini, D.; Sarkar, M.; Sasada, T.; Saxena, N.K.; Shackelford, R.E.; Kumara, H.M.C.S.; Sharma, D.; Shin, D.M.; Sidransky, D.; Siegelin, M.D.; Signori, E.; Singh, N.; Sivanand, S.; Sliva, D.; Smythe, C.; Spagnuolo, C.; Stafforini, D.M.; Stagg, J.; Sub-barayan, P.R.; Sundin, T.; Talib, W.H.; Thompson, S.K.; Tran, P.T.; Ungefroren, H.; Heiden, M.G.V.; Venkateswaran, V.; Vinay, D.S.; Vlachostergios, P.J.; Wang, Z.; Wel-len, K.E.; Whelan, R.L.; Yang, E.S.; Yang, H.; Yang, X.; Yaswen, P.; Yedjou, C.; Yin, X.; Zhu, J.; Zollo, M. Designing a broad-spectrum integrative approach for cancer prevention and treatment. Semin. Cancer Biol., 2015, 35(Suppl.), S276-S304.
[http://dx.doi.org/10.1016/j.semcancer.2015.09.007]

Aguayo, A.; Cortes, J.; Thomas, D.; Pierce, S.; Keating, M.; Kantarjian, H. Combination therapy with methotrexate, vincristine, polyethylene-glycol conjugated-asparaginase, and prednisone in the treatment of patients with refractory or recurrent acute lymphoblastic leukemia. Cancer, 1999, 86(7), 1203-1209.
[http://dx.doi.org/10.1002/(SICI)1097-0142(19991001)86:7<1203:AID-CNCR15>3.0.CO;2-3] [PMID: 10506705]

Capizzi, R.L. Schedule-dependent synergism and antagonism between methotrexate and asparaginase. In: Symposium on Clinical Pharmacology; Creasy, W.A.; Lane, M.; Sartorelli, A.C., Eds.; , 1975; pp. 151-161.
[http://dx.doi.org/10.1016/B978-0-08-018949-9.50020-8]

Capizzi, R.L. Asparaginase-methotrexate in combination chemotherapy: Schedule-dependent differential effects on normal versus neoplastic cells. Cancer Treat. Rep., 1981, 65(Suppl. 4), 115-121.
[PMID: 7049375]

Sur, P.; Fernandes, D.J.; Kute, T.E.; Capizzi, R.L. L-asparaginase-induced modulation of methotrexate polyglutamylation in murine leukemia L5178Y. Cancer Res., 1987, 47(5), 1313-1318.
[PMID: 2434214]

Vadlamudi, S.; Krishna, B.; Reddy, V.V.; Goldin, A. Schedule-dependent therapeutic synergism for L-asparaginase and methotrexate in leukemic (L5178Y) mice. Cancer Res., 1973, 33(9), 2014-2019.
[PMID: 4725366]

Jolivet, J.; Cole, D.E.; Holcenberg, J.S.; Poplack, D.G. Prevention of methotrexate cytotoxicity by asparaginase inhibition of methotrexate polyglutamate formation. Cancer Res., 1985, 45(1), 217-220.
[PMID: 2578094]

Lobel, J.S.; O’Brien, R.T.; McIntosh, S.; Aspnes, G.T.; Capizzi, R.L. Methotrexate and asparaginase combination chemotherapy in refractory acute lymphoblastic leuke-mia of childhood. Cancer, 1979, 43(3), 1089-1094.
[http://dx.doi.org/10.1002/1097-0142(197903)43:3<1089:AID-CNCR2820430346>3.0.CO;2-H] [PMID: 284840]

Ortega, J.A.; Nesbit, M.E. Jr.; Donaldson, M.H.; Hittle, R.E.; Weiner, J.; Karon, M.; Hammond, D. L-Asparaginase, vincristine, and prednisone for induction of first remission in acute lymphocytic leukemia. Cancer Res., 1977, 37(2), 535-540.
[PMID: 264412]

Wei, N.; Fu, L.; Wang, J.; Wang, Z. Pegylated asparaginase in combination with vincristine, daunorubicin and prednisone for remission induction in adult acute lympho-blastic leukaemia. Blood, 2013, 122(21), 5020.
[http://dx.doi.org/10.1182/blood.V122.21.5020.5020]

Kadia, T.M.; Kantarjian, H.M.; Thomas, D.A.; O’Brien, S.; Estrov, Z.; Ravandi, F.; Jabbour, E.; Pemmaraju, N.; Daver, N.; Wang, X.; Jain, P.; Pierce, S.; Brandt, M.; Garcia-Manero, G.; Cortes, J.; Borthakur, G. Phase II study of methotrexate, vincristine, pegylated-asparaginase, and dexamethasone (MOpAD) in patients with re-lapsed/refractory acute lymphoblastic leukemia. Am. J. Hematol., 2015, 90(2), 120-124.
[http://dx.doi.org/10.1002/ajh.23886] [PMID: 25368968]

Chiu, M.; Taurino, G.; Bianchi, M.G.; Kilberg, M.S.; Bussolati, O. Asparagine synthetase in cancer: Beyond acute lymphoblastic leukemia. Front. Oncol., 2020, 9, 1480.
[http://dx.doi.org/10.3389/fonc.2019.01480] [PMID: 31998641]

Tallal, L.; Tan, C.; Oettgen, H.; Wollner, N.; McCarthy, M.; Helson, L.; Burchenal, J.; Karnofsky, D.; Murphy, M.L.E. coli L-asparaginase in the treatment of leukemia and solid tumors in 131 children. Cancer, 1970, 25(2), 306-320.
[http://dx.doi.org/10.1002/1097-0142(197002)25:2<306:AID-CNCR2820250206>3.0.CO;2-H] [PMID: 4905155]

Asselin, B.L. The three asparaginases. Comparative pharmacology and optimal use in childhood leukemia. Adv. Exp. Med. Biol., 1999, 457, 621-629.
[http://dx.doi.org/10.1007/978-1-4615-4811-9_69] [PMID: 10500842]

Riccardi, R.; Holcenberg, J.S.; Glaubiger, D.L.; Wood, J.H.; Poplack, D.G. L-asparaginase pharmacokinetics and asparagine levels in cerebrospinal fluid of rhesus mon-keys and humans. Cancer Res., 1981, 41(11 Pt 1), 4554-4558.
[PMID: 6895481]

Earl, M. Incidence and management of asparaginase-associated adverse events in patients with acute lymphoblastic leukemia. Clin. Adv. Hematol. Oncol., 2009, 7(9), 600-606.
[PMID: 20020672]

Hijiya, N.; van der Sluis, I.M. Asparaginase-associated toxicity in children with acute lymphoblastic leukemia. Leuk. Lymphoma, 2016, 57(4), 748-757.
[http://dx.doi.org/10.3109/10428194.2015.1101098] [PMID: 26457414]

Schmidt, M.P.; Ivanov, A.V.; Coriu, D.; Miron, I.C. L-Asparaginase toxicity in the treatment of children and adolescents with acute lymphoblastic leukemia. J. Clin. Med., 2021, 10(19), 4419.
[http://dx.doi.org/10.3390/jcm10194419]

Stock, W.; Douer, D.; DeAngelo, D.J.; Arellano, M.; Advani, A.; Damon, L.; Kovacsovics, T.; Litzow, M.; Rytting, M.; Borthakur, G.; Bleyer, A. Prevention and manage-ment of asparaginase/pegasparaginase-associated toxicities in adults and older adolescents: recommendations of an expert panel. Leuk. Lymphoma, 2011, 52(12), 2237-2253.
[http://dx.doi.org/10.3109/10428194.2011.596963] [PMID: 21827361]

Stock, W.; Luger, S.M.; Advani, A.S.; Yin, J.; Harvey, R.C.; Mullighan, C.G.; Willman, C.L.; Fulton, N.; Laumann, K.M.; Malnassy, G.; Paietta, E.; Parker, E.; Geyer, S.; Mrózek, K.; Bloomfield, C.D.; Sanford, B.; Marcucci, G.; Liedtke, M.; Claxton, D.F.; Foster, M.C.; Bogart, J.A.; Grecula, J.C.; Appelbaum, F.R.; Erba, H.; Litzow, M.R.; Tallman, M.S.; Stone, R.M.; Larson, R.A. A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: Results of CALGB 10403. Blood, 2019, 133(14), 1548-1559.
[http://dx.doi.org/10.1182/blood-2018-10-881961] [PMID: 30658992]

Elliott, M.A.; Wolf, R.C.; Hook, C.C.; Pruthi, R.K.; Heit, J.A.; Letendre, L.L.; Tefferi, A.; Kaufmann, S.H.; Mesa, R.A.; Litzow, M.R. Thromboembolism in adults with acute lymphoblastic leukemia during induction with L-asparaginase-containing multi-agent regimens: Incidence, risk factors, and possible role of antithrombin. Leuk. Lymphoma, 2004, 45(8), 1545-1549.
[http://dx.doi.org/10.1080/10428190410001693588] [PMID: 15370205]

Caruso, V.; Iacoviello, L.; Di Castelnuovo, A.; Storti, S.; Mariani, G.; de Gaetano, G.; Donati, M.B. Thrombotic complications in childhood acute lymphoblastic leuke-mia: A meta-analysis of 17 prospective studies comprising 1752 pediatric patients. Blood, 2006, 108(7), 2216-2222.
[http://dx.doi.org/10.1182/blood-2006-04-015511] [PMID: 16804111]

Burke, P.W.; Hoelzer, D.; Park, J.H.; Schmiegelow, K.; Douer, D. Managing toxicities with asparaginase-based therapies in adult all: Summary of an ESMO open-cancer horizons roundtable discussion. ESMO Open, 2020, 5(5), e000858.
[http://dx.doi.org/10.1136/esmoopen-2020-000858] [PMID: 33037033]

Wacker, P.; Land, V.J.; Camitta, B.M.; Kurtzberg, J.; Pullen, J.; Harris, M.B.; Shuster, J.J. Children’s Oncology Study Group. Allergic reactions to E. coli L-asparaginase do not affect outcome in childhood B-precursor acute lymphoblastic leukemia: A Children’s Oncology Group Study. J. Pediatr. Hematol. Oncol., 2007, 29(9), 627-632.
[http://dx.doi.org/10.1097/MPH.0b013e3181483df1] [PMID: 17805038]

Kieslich, M.; Porto, L.; Lanfermann, H.; Jacobi, G.; Schwabe, D.; Böhles, H. Cerebrovascular complications of L-asparaginase in the therapy of acute lymphoblastic leukemia. J. Pediatr. Hematol. Oncol., 2003, 25(6), 484-487.
[http://dx.doi.org/10.1097/00043426-200306000-00011] [PMID: 12794528]

Merryman, R.; Stevenson, K.E.; Gostic, W.J. II.; Neuberg, D.; O’Brien, J.; Sallan, S.E.; Silverman, L.B. Asparaginase-associated myelosuppression and effects on dosing of other chemotherapeutic agents in childhood acute lymphoblastic leukemia. Pediatr. Blood Cancer, 2012, 59(5), 925-927.
[http://dx.doi.org/10.1002/pbc.24182] [PMID: 22532399]

Gerson, S.L.; Caimi, P.F.; William, B.M.; Creger, R.J. Pharmacology and molecular mechanisms of antineoplastic agents for hematologic malignancies. In: Hematology; Hoffman, R.; Benz, E.J.Jr; Silberstein, L.E.; Heslop, H.E.; Weitz, J.I.; Anatasi, J.; Salama, M.E.; Abutalib, S.A., Eds.; , 2018, pp. 849-912.
[http://dx.doi.org/10.1016/B978-0-323-35762-3.00057-3]

Raja, R.A.; Schmiegelow, K.; Frandsen, T.L. Asparaginase-associated pancreatitis in children. Br. J. Haematol., 2012, 159(1), 18-27.
[http://dx.doi.org/10.1111/bjh.12016] [PMID: 22909259]

Zenatti, P.P.; Migita, N.A.; Cury, N.M.; Mendes-Silva, R.A.; Gozzo, F.C.; de Campos-Lima, P.O.; Yunes, J.A.; Brandalise, S.R. Low bioavailability and high immunogen-icity of a new brand of E. coli L-asparaginase with active host contaminating proteins. EBioMedicine, 2018, 30, 158-166.
[http://dx.doi.org/10.1016/j.ebiom.2018.03.005] [PMID: 29550241]

Battistel, A.P.; da Rocha, B.S.; Santos, M.T.D.; Daudt, L.E.; Michalowski, M.B. Allergic reactions to asparaginase: retrospective cohort study in pediatric patients with acute lymphoid leukemia. Hematol. Transfus. Cell Ther., 2021, 43(1), 9-14.
[http://dx.doi.org/10.1016/j.htct.2019.10.007] [PMID: 32014473]

Pieters, R.; Hunger, S.P.; Boos, J.; Rizzari, C.; Silverman, L.; Baruchel, A.; Goekbuget, N.; Schrappe, M.; Pui, C.H. L-asparaginase treatment in acute lymphoblastic leuke-mia: A focus on Erwinia asparaginase. Cancer, 2011, 117(2), 238-249.
[http://dx.doi.org/10.1002/cncr.25489] [PMID: 20824725]

Asselin, B.; Rizzari, C. Asparaginase pharmacokinetics and implications of therapeutic drug monitoring. Leuk. Lymphoma, 2015, 56(8), 2273-2280.
[http://dx.doi.org/10.3109/10428194.2014.1003056] [PMID: 25586605]

Boos, J.; Werber, G.; Ahlke, E.; Schulze-Westhoff, P.; Nowak-Göttl, U.; Würthwein, G.; Verspohl, E.J.; Ritter, J.; Jürgens, H. Monitoring of asparaginase activity and asparagine levels in children on different asparaginase preparations. Eur. J. Cancer, 1996, 32A(9), 1544-1550.
[http://dx.doi.org/10.1016/0959-8049(96)00131-1] [PMID: 8911116]

Billett, A.L.; Carls, A.; Gelber, R.D.; Sallan, S.E. Allergic reactions to Erwinia asparaginase in children with acute lymphoblastic leukemia who had previous allergic reactions to Escherichia coli asparaginase. Cancer, 1992, 70(1), 201-206.
[http://dx.doi.org/10.1002/1097-0142(19920701)70:1<201:AID-CNCR2820700131>3.0.CO;2-M] [PMID: 1606543]

Vrooman, L.M.; Supko, J.G.; Neuberg, D.S.; Asselin, B.L.; Athale, U.H.; Clavell, L.; Kelly, K.M.; Laverdière, C.; Michon, B.; Schorin, M.; Cohen, H.J.; Sallan, S.E.; Silverman, L.B. Erwinia asparaginase after allergy to E. coli asparaginase in children with acute lymphoblastic leukemia. Pediatr. Blood Cancer, 2010, 54(2), 199-205.
[http://dx.doi.org/10.1002/pbc.22225] [PMID: 19672973]

Fu, C.H.; Sakamoto, K.M. PEG-asparaginase. Expert Opin. Pharmacother., 2007, 8(12), 1977-1984.
[http://dx.doi.org/10.1517/14656566.8.12.1977] [PMID: 17696798]

Heo, Y.A.; Syed, Y.Y.; Keam, S.J. Pegaspargase: A review in acute lymphoblastic leukaemia. Drugs, 2019, 79(7), 767-777.
[http://dx.doi.org/10.1007/s40265-019-01120-1] [PMID: 31030380]

Silverman, L.B.; Gelber, R.D.; Dalton, V.K.; Asselin, B.L.; Barr, R.D.; Clavell, L.A.; Hurwitz, C.A.; Moghrabi, A.; Samson, Y.; Schorin, M.A.; Arkin, S.; Declerck, L.; Cohen, H.J.; Sallan, S.E. Improved outcome for children with acute lymphoblastic leukemia: Results of Dana-Farber consortium protocol 91-01. Blood, 2001, 97(5), 1211-1218.
[http://dx.doi.org/10.1182/blood.V97.5.1211] [PMID: 11222362]

Armstrong, J.K.; Hempel, G.; Koling, S.; Chan, L.S.; Fisher, T.; Meiselman, H.J.; Garratty, G. Antibody against poly(ethylene glycol) adversely affects PEG-asparaginase therapy in acute lymphoblastic leukemia patients. Cancer, 2007, 110(1), 103-111.
[http://dx.doi.org/10.1002/cncr.22739] [PMID: 17516438]

Modi, T.; Gervais, D. Improved pharmacokinetic and pharmacodynamic profile of a novel PEGylated native Erwinia chrysanthemi L-asparaginase. Invest. New Drugs, 2021. [A head of print
[http://dx.doi.org/10.1007/s10637-021-01173-8]

Schauer, P.; Arlin, Z.A.; Mertelsmann, R.; Cirrincione, C.; Friedman, A.; Gee, T.S.; Dowling, M.; Kempin, S.; Straus, D.J.; Koziner, B. Treatment of acute lymphoblastic leukemia in adults: Results of the L-10 and L-10M protocols. J. Clin. Oncol., 1983, 1(8), 462-470.
[http://dx.doi.org/10.1200/JCO.1983.1.8.462] [PMID: 6583321]

Lister, T.A.; Whitehouse, J.M.; Beard, M.E.; Brearley, R.L.; Wrigley, P.F.; Oliver, R.T.; Freeman, J.E.; Woodruff, R.K.; Malpas, J.S.; Paxton, A.M.; Crowther, D. Combina-tion chemotherapy for acute lymphoblastic leukaemia in adults. Br. Med. J., 1978, 1(6107), 199-203.
[http://dx.doi.org/10.1136/bmj.1.6107.199] [PMID: 271516]

Marcus, R.E.; Catovsky, D.; Johnson, S.A.; Gregory, W.M.; Talavera, J.G.; Goldman, J.M.; Galton, D.A. Adult acute lymphoblastic leukaemia: A study of prognostic features and response to treatment over a ten year period. Br. J. Cancer, 1986, 53(2), 175-180.
[http://dx.doi.org/10.1038/bjc.1986.32] [PMID: 3456786]

Hoelzer, D.; Thiel, E.; Löffler, H.; Büchner, T.; Ganser, A.; Heil, G.; Koch, P.; Freund, M.; Diedrich, H.; Rühl, H.; Maschmeyer, G.; Lipp, T.; Nowrousian, M.R.; Burkert, M.; Gerecke, D.; Pralle, H.; Muller, U.; Lunscken, C.; Fulle, H.; Ho, A.D. Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood, 1988, 71(1), 123-131.
[http://dx.doi.org/10.1182/blood.V71.1.123.123] [PMID: 3422030]

Durrant, I.J.; Richards, S.M. Results of medical research council trial UKALL IX in acute lymphoblastic leukaemia in adults: Report from the medical research council working party on adult leukaemia. Br. J. Haematol., 1993, 85(1), 84-92.
[http://dx.doi.org/10.1111/j.1365-2141.1993.tb08649.x] [PMID: 8251413]

Hussein, K.K.; Dahlberg, S.; Head, D.; Waddell, C.C.; Dabich, L.; Weick, J.K.; Morrison, F.; Saiki, J.H.; Metz, E.; Rivkin, S.E. Treatment of acute lymphoblastic leukemia in adults with intensive induction, consolidation, and maintenance chemotherapy. Blood, 1989, 73(1), 57-63.
[http://dx.doi.org/10.1182/blood.V73.1.57.57] [PMID: 2642717]

Linker, C.A.; Levitt, L.J.; O’Donnell, M.; Forman, S.J.; Ries, C.A. Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: A follow-up report. Blood, 1991, 78(11), 2814-2822.
[http://dx.doi.org/10.1182/blood.V78.11.2814.2814] [PMID: 1835410]

Ellison, R.R.; Mick, R.; Cuttner, J.; Schiffer, C.A.; Silver, R.T.; Henderson, E.S.; Woliver, T.; Royston, I.; Davey, F.R.; Glicksman, A.S.; Bloomfield, C.D.; Holland, J.F. The effects of postinduction intensification treatment with cytarabine and daunorubicin in adult acute lymphocytic leukemia: A prospective randomized clinical trial by cancer and leukemia group B. J. Clin. Oncol., 1991, 9(11), 2002-2015.
[http://dx.doi.org/10.1200/JCO.1991.9.11.2002] [PMID: 1941059]

Rowe, J.M.; Buck, G.; Burnett, A.K.; Chopra, R.; Wiernik, P.H.; Richards, S.M.; Lazarus, H.M.; Franklin, I.M.; Litzow, M.R.; Ciobanu, N.; Prentice, H.G.; Durrant, J.; Tallman, M.S.; Goldstone, A.H. ECOG; MRC/NCRI Adult Leukemia Working Party. Induction therapy for adults with acute lymphoblastic leukemia: Results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood, 2005, 106(12), 3760-3767.
[http://dx.doi.org/10.1182/blood-2005-04-1623] [PMID: 16105981]

Huguet, F.; Leguay, T.; Raffoux, E.; Thomas, X.; Beldjord, K.; Delabesse, E.; Chevallier, P.; Buzyn, A.; Delannoy, A.; Chalandon, Y.; Vernant, J.P.; Lafage-Pochitaloff, M.; Chassevent, A.; Lhéritier, V.; Macintyre, E.; Béné, M.C.; Ifrah, N.; Dombret, H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: The GRAALL-2003 study. J. Clin. Oncol., 2009, 27(6), 911-918.
[http://dx.doi.org/10.1200/JCO.2008.18.6916] [PMID: 19124805]

Ribera, J.M.; Oriol, A.; Sanz, M.A.; Tormo, M.; Fernández-Abellán, P.; del Potro, E.; Abella, E.; Bueno, J.; Parody, R.; Bastida, P.; Grande, C.; Heras, I.; Bethencourt, C.; Feliu, E.; Ortega, J.J. Comparison of the results of the treatment of adolescents and young adults with standard-risk acute lymphoblastic leukemia with the programa Es-pañol de tratamiento en hematología pediatric-based protocol all-96. J. Clin. Oncol., 2008, 26(11), 1843-1849.
[http://dx.doi.org/10.1200/JCO.2007.13.7265] [PMID: 18398150]

Sikorska-Fic, B.; Makowska, K.; Rokicka-Milewska, R. The use of PEG-asparaginase in leukemic children with prior hypersensitivity to native L-asparaginase. In: Acute Leukemias; VIII; Büchner, T.; Hiddemann, W.; Wörmann, B.; Schellong, G.; Ritter, J.; Creutzig, U., Eds.; Springer: Berlin, Heidelberg, 2001, Vol. 40, pp. 381-383.
[http://dx.doi.org/10.1007/978-3-642-18156-6_62]

Park, Y.K.; Abuchowski, A.; Davis, S.; Davis, F. Pharmacology of Escherichia coli-L-asparaginase polyethylene glycol adduct. Anticancer Res., 1981, 1(6), 373-376.
[PMID: 7046623]

Douer, D.; Yampolsky, H.; Cohen, L.J.; Watkins, K.; Levine, A.M.; Periclou, A.P.; Avramis, V.I. Pharmacodynamics and safety of intravenous pegaspargase during re-mission induction in adults aged 55 years or younger with newly diagnosed acute lymphoblastic leukemia. Blood, 2007, 109(7), 2744-2750.
[http://dx.doi.org/10.1182/blood-2006-07-035006] [PMID: 17132721]

Rytting, M.; Earl, M.; Douer, D.; Muriera, B.; Advani, A.; Bleyer, A. Toxicities in adults with acute lymphoblastic leukemia (ALL) treated with regimens using pegaspar-aginase. Blood, 2008, 112(11), 1924.
[http://dx.doi.org/10.1182/blood.V112.11.1924.1924]

Patel, B.; Kirkwood, A.A.; Dey, A.; Marks, D.I.; McMillan, A.K.; Menne, T.F.; Micklewright, L.; Patrick, P.; Purnell, S.; Rowntree, C.J.; Smith, P.; Fielding, A.K. Pegylat-ed-asparaginase during induction therapy for adult acute lymphoblastic leukaemia: Toxicity data from the UKALL14 trial. Leukemia, 2017, 31(1), 58-64.
[http://dx.doi.org/10.1038/leu.2016.219] [PMID: 27480385]

Pasut, G.; Veronese, F.M. PEG conjugates in clinical development or use as anticancer agents: An overview. Adv. Drug Deliv. Rev., 2009, 61(13), 1177-1188.
[http://dx.doi.org/10.1016/j.addr.2009.02.010] [PMID: 19671438]

Kloos, R.; van der Sluis, I.M.; Mastrobattista, E.; Hennink, W.; Pieters, R.; Verhoef, J.J. Acute lymphoblastic leukaemia patients treated with PEGasparaginase develop antibodies to PEG and the succinate linker. Br. J. Haematol., 2020, 189(3), 442-451.
[http://dx.doi.org/10.1111/bjh.16254] [PMID: 31883112]

Cecconello, D.K.; de Magalhães, M.R.; Werlang, I.C.R.; de Martino Lee, M.L.; Michalowski, M.B.; Daudt, L.E. Asparaginase: An old drug with new questions. Hematol. Transfus. Cell Ther., 2020, 42(3), 275-282.
[http://dx.doi.org/10.1016/j.htct.2019.07.010] [PMID: 31801703]

Ogawa, C.; Manabe, A.; Goto, H.; Koh, K.; Tomizawa, D.; Fukushima, K.; Watanabe, K.; Horibe, K.; Kikuta, A.; Hamada, M.; Ohara, A. Phase I/II clinical trial of Erwinia asparaginase (ErwinaseR) in combination with prednisolone, vincristine and pirarubicin in children and young adults with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL). Blood, 2014, 124(21), 3657.
[http://dx.doi.org/10.1182/blood.V124.21.3657.3657]

Horvat, T.Z.; Pecoraro, J.J.; Daley, R.J.; Buie, L.W.; King, A.C.; Rampal, R.K.; Tallman, M.S.; Park, J.H.; Douer, D. The use of Erwinia asparaginase for adult patients with acute lymphoblastic leukemia after pegaspargase intolerance. Leuk. Res., 2016, 50, 17-20.
[http://dx.doi.org/10.1016/j.leukres.2016.08.014] [PMID: 27631159]

Romero, M.M.V.; Gil, S.G.; Casariego, G.J.N.; Alonso, J.M.; Nicolás, F.G. Activity of Erwinia-asparaginase after anaphylactic reaction to Peg-asparaginase. An. Pediatría (English Ed.), 2019. 90, pp. (3)187-188.
[http://dx.doi.org/10.1016/j.anpede.2018.03.012]

Lin, T.; Hernandez-Illas, M.; Rey, A.; Jenkins, J.; Chandula, R.; Silverman, J.A.; Choi, M.R. A randomized phase I study to evaluate the safety, tolerability, and pharma-cokinetics of recombinant Erwinia asparaginase (JZP-458) in healthy adult volunteers. Clin. Transl. Sci., 2021, 14(3), 870-879.
[http://dx.doi.org/10.1111/cts.12947] [PMID: 33278328]

Maese, L.; Rau, R.E.; Raetz, E.A.; Lin, T.; Kim, P.; Chandula, R.; McClung, S.; Gray, J.; Choi, L.M.R.; Loh, M.L.; Adamson, P.C. A Phase II/III study of JZP-458 in pa-tients with acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL) who are hypersensitive to E. coli-derived asparaginases. J. Clin. Oncol., 2020, 38(15)(Suppl.)
[http://dx.doi.org/10.1200/JCO.2020.38.15_suppl.TPS7568]

U.S Food and Drug. FDA DISCO Burst Edition: FDA approves Rylaze (Asparaginase Erwinia chrysanthemi (recombinant) - rywn) for treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma in adult and pediatric patients 1 month or older who have developed hypersensitivity to E. coli-derived asparaginase. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-disco-burst-edition-fda-approves-rylaze-asparaginase-erwinia-chrysanthemi-recombinant-rywn (accessed on: Oct 16, 2021).

Hewitt, M.; Weiner, S. L.; Simone, J. V. The epidemiology of childhood cancer, 2003.

Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer Statistics, 2017. CA Cancer J. Clin., 2017, 67(1), 7-30.
[http://dx.doi.org/10.3322/caac.21387] [PMID: 28055103]

Takahashi, H.; Koh, K.; Kato, M.; Isobe, K.; Yasui, N.; Mori, M.; Akiyama, K.; Kikuchi, A.; Hanada, R. The feasibility of Erwinia asparaginase for pediatric patients who developed an allergic reaction to E.coli asparaginase during treatment of acute lymphoblastic leukemia. Rinsho Ketsueki, 2013, 54(4), 370-377.
[http://dx.doi.org/10.11406/rinketsu.54.370] [PMID: 23666219]

Salzer, W.L.; Asselin, B.; Supko, J.G.; Devidas, M.; Kaiser, N.A.; Plourde, P.; Winick, N.J.; Reaman, G.H.; Raetz, E.; Carroll, W.L.; Hunger, S.P. Erwinia asparaginase achieves therapeutic activity after pegaspargase allergy: A report from the children’s oncology group. Blood, 2013, 122(4), 507-514.
[http://dx.doi.org/10.1182/blood-2013-01-480822] [PMID: 23741010]

Ko, R.H.; Jones, T.L.; Radvinsky, D.; Robison, N.; Gaynon, P.S.; Panosyan, E.H.; Avramis, I.A.; Avramis, V.I.; Rubin, J.; Ettinger, L.J.; Seibel, N.L.; Dhall, G. Allergic reactions and antiasparaginase antibodies in children with high-risk acute lymphoblastic leukemia: A children’s oncology group report. Cancer, 2015, 121(23), 4205-4211.
[http://dx.doi.org/10.1002/cncr.29641] [PMID: 26308766]

Woo, M.H.; Hak, L.J.; Storm, M.C.; Sandlund, J.T.; Ribeiro, R.C.; Rivera, G.K.; Rubnitz, J.E.; Harrison, P.L.; Wang, B.; Evans, W.E.; Pui, C.H.; Relling, M.V. Hypersensi-tivity or development of antibodies to asparaginase does not impact treatment outcome of childhood acute lymphoblastic leukemia. J. Clin. Oncol., 2000, 18(7), 1525-1532.
[http://dx.doi.org/10.1200/JCO.2000.18.7.1525] [PMID: 10735901]

Verma, A.; Chen, K.; Bender, C.; Gorney, N.; Leonard, W.; Barnette, P. PEGylated E. coli asparaginase desensitization: An effective and feasible option for pediatric patients with acute lymphoblastic leukemia who have developed hypersensitivity to pegaspargase in the absence of asparaginase Erwinia chrysanthemi availability. Pediatr. Hematol. Oncol., 2019, 36(5), 277-286.
[http://dx.doi.org/10.1080/08880018.2019.1634778] [PMID: 31296092]

Mondelaers, V.; Ferster, A.; Uyttebroeck, A.; Brichard, B.; Werff ten Bosch, J.; Norga, K.; Francotte, N.; Piette, C.; Vandemeulebroecke, K.; Verbeke, C.; Schmidt, S.; Benoit, Y.; Lammens, T.; De Moerloose, B. Prospective, real-time monitoring of pegylated Escherichia coli and Erwinia asparaginase therapy in childhood acute lym-phoblastic leukaemia and non-Hodgkin lymphoma in Belgium. Br. J. Haematol., 2020.
[http://dx.doi.org/10.1111/bjh.16495]

Kloos, R.Q.H.; Pieters, R.; Jumelet, F.M.V.; de Groot-Kruseman, H.A.; van den Bos, C.; van der Sluis, I.M. Individualized asparaginase dosing in childhood acute lym-phoblastic leukemia. J. Clin. Oncol., 2020, 38(7), 715-724.
[http://dx.doi.org/10.1200/JCO.19.02292] [PMID: 31922920]

Cecconello, D.K.; Rechenmacher, C.; Werlang, I.; Zenatti, P.P.; Yunes, J.A.; Alegretti, A.P.; Lanvers-Kaminsky, C.; Daudt, L.E.; Michalowski, M.B. Implementation of the asparaginase activity assessment technique for clinical use: Experience of a Brazilian center. Sci. Rep., 2020, 10(1), 1-6.
[http://dx.doi.org/10.1038/s41598-020-78549-y]

Gottschalk Højfeldt, S.; Grell, K.; Abrahamsson, J.; Lund, B.; Vettenranta, K.; Jónsson, Ó.G.; Frandsen, T.L.; Wolthers, B.O.; Marquart, H.V.; Vaitkeviciene, G.; Lepik, K.; Heyman, M.; Schmiegelow, K.; Albertsen, B.K. Relapse risk following truncation of pegylated asparaginase in childhood acute lymphoblastic leukemia. Blood, 2021, 137(17), 2373-2382.
[http://dx.doi.org/10.1182/blood.2020006583] [PMID: 33150360]

Duval, M.; Suciu, S.; Ferster, A.; Rialland, X.; Nelken, B.; Lutz, P.; Benoit, Y.; Robert, A.; Manel, A-M.; Vilmer, E.; Otten, J.; Philippe, N. Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer-Children’s Leukemia Group phase 3 trial. Blood, 2002, 99(8), 2734-2739.
[http://dx.doi.org/10.1182/blood.V99.8.2734] [PMID: 11929760]

Vieira Pinheiro, J.P.; Lanversa, C.; Würthwein, G.; Beier, R.; Casimiro da Palma, J.; von Stackelberg, A.; Boos, J. Drug monitoring of PEG-asparaginase treatment in childhood acute lymphoblastic leukemia and non-Hodgkin’s lymphoma. Leuk. Lymphoma, 2002, 43(10), 1911-1920.
[http://dx.doi.org/10.1080/1042819021000015853] [PMID: 12481884]

Perel, Y.; Auvrignon, A.; Leblanc, T.; Vannier, J-P.; Michel, G.; Nelken, B.; Gandemer, V.; Schmitt, C.; Lamagnere, J-P.; De Lumley, L.; Bader-Meunier, B.; Couillaud, G.; Schaison, G.; Landman-Parker, J.; Thuret, I.; Dalle, J-H.; Baruchel, A.; Leverger, G. Group LAME of the French Society of Pediatric Hematology and Immunology. Impact of addition of maintenance therapy to intensive induction and consolidation chemotherapy for childhood acute myeloblastic leukemia: results of a prospective random-ized trial, LAME 89/91. Leucámie Aiqüe Myéloïde Enfant. J. Clin. Oncol., 2002, 20(12), 2774-2782.
[http://dx.doi.org/10.1200/JCO.2002.07.300] [PMID: 12065553]

Ando, M.; Sugimoto, K.; Kitoh, T.; Sasaki, M.; Mukai, K.; Ando, J.; Egashira, M.; Schuster, S.M.; Oshimi, K. Selective apoptosis of natural killer-cell tumours by l-asparaginase. Br. J. Haematol., 2005, 130(6), 860-868.
[http://dx.doi.org/10.1111/j.1365-2141.2005.05694.x] [PMID: 16156856]

Ishida, F.; Ko, Y.H.; Kim, W.S.; Suzumiya, J.; Isobe, Y.; Oshimi, K.; Nakamura, S.; Suzuki, R. Aggressive natural killer cell leukemia: therapeutic potential of L-asparaginase and allogeneic hematopoietic stem cell transplantation. Cancer Sci., 2012, 103(6), 1079-1083.
[http://dx.doi.org/10.1111/j.1349-7006.2012.02251.x] [PMID: 22360679]

Bu, S.; Yuan, F.; Wei, X.; Yin, Q.; Li, Y.; Mi, R.; Yang, H.; Li, H.; Ge, S.; Liu, Y.; Song, Y. L-asparaginase-based regimen as a first-line treatment for newly diagnosed nasal type extranodal natural killer cell/T-cell lymphoma. Exp. Ther. Med., 2016, 11(6), 2437-2445.
[http://dx.doi.org/10.3892/etm.2016.3249] [PMID: 27313673]

Lorenzi, P.L.; Reinhold, W.C.; Rudelius, M.; Gunsior, M.; Shankavaram, U.; Bussey, K.J.; Scherf, U.; Eichler, G.S.; Martin, S.E.; Chin, K.; Gray, J.W.; Kohn, E.C.; Horak, I.D.; Von Hoff, D.D.; Raffeld, M.; Goldsmith, P.K.; Caplen, N.J.; Weinstein, J.N. Asparagine synthetase as a causal, predictive biomarker for L-asparaginase activity in ovarian cancer cells. Mol. Cancer Ther., 2006, 5(11), 2613-2623.
[http://dx.doi.org/10.1158/1535-7163.MCT-06-0447] [PMID: 17088436]

Cappelletti, D.; Chiarelli, L.R.; Pasquetto, M.V.; Stivala, S.; Valentini, G.; Scotti, C. Helicobacter pyloril-asparaginase: a promising chemotherapeutic agent. Biochem. Biophys. Res. Commun., 2008, 377(4), 1222-1226.
[http://dx.doi.org/10.1016/j.bbrc.2008.10.118] [PMID: 18983825]

Scotti, C.; Sommi, P.; Pasquetto, M.V.; Cappelletti, D.; Stivala, S.; Mignosi, P.; Savio, M.; Chiarelli, L.R.; Valentini, G.; Bolanos-Garcia, V.M.; Merrell, D.S.; Franchini, S.; Verona, M.L.; Bolis, C.; Solcia, E.; Manca, R.; Franciotta, D.; Casasco, A.; Filipazzi, P.; Zardini, E.; Vannini, V. Cell-cycle inhibition by Helicobacter pylori L-asparaginase. PLoS One, 2010, 5(11), e13892.
[http://dx.doi.org/10.1371/journal.pone.0013892] [PMID: 21085483]

Yu, Q.; Wang, X.; Wang, L.; Zheng, J.; Wang, J.; Wang, B. Knockdown of asparagine synthetase (ASNS) suppresses cell proliferation and inhibits tumor growth in gastric cancer cells. Scand. J. Gastroenterol., 2016, 51(10), 1220-1226.
[http://dx.doi.org/10.1080/00365521.2016.1190399] [PMID: 27251594]

Sindhu, R.; Manonmani, H.K. L-asparaginase induces intrinsic mitochondrial-mediated apoptosis in human gastric adenocarcinoma cells and impedes tumor progres-sion. Biochem. Biophys. Res. Commun., 2018, 503(4), 2393-2399.
[http://dx.doi.org/10.1016/j.bbrc.2018.06.167] [PMID: 29966654]

Do, T.T.; Do, T.P.; Nguyen, T.N.; Nguyen, T.C.; Vu, T.T.P.; Nguyen, T.G.A.; Quang Khieu, D. Nanoliposomal L-asparaginase and its antitumor activities in lewis lung carcinoma tumor-induced BALB/c mice. Adv. Mater. Sci. Eng., 2019.
[http://dx.doi.org/10.1155/2019/3534807]

Borges, G.Á.; Elias, S.T.; Araujo, T.S.; Souza, P.M.; Nascimento-Filho, C.H.V.; Castilho, R.M.; Squarize, C.H.; Magalhães, P.O.; Guerra, E.N.S. Asparaginase induces selective dose- and time-dependent cytotoxicity, apoptosis, and reduction of NFκB expression in oral cancer cells. Clin. Exp. Pharmacol. Physiol., 2020, 47(5), 857-866.
[http://dx.doi.org/10.1111/1440-1681.13256] [PMID: 31943292]

Apfel, V.; Begue, D.; Cordo’, V.; Holzer, L.; Martinuzzi, L.; Buhles, A.; Kerr, G.; Barbosa, I.; Naumann, U.; Piquet, M.; Ruddy, D.; Weiss, A.; Ferretti, S.; Almeida, R.; Bonenfant, D.; Tordella, L.; Galli, G.G. Therapeutic assessment of targeting ASNS combined with L-asparaginase treatment in solid tumors and investigation of re-sistance mechanisms. ACS Pharmacol. Transl. Sci., 2021, 4(1), 327-337.
[http://dx.doi.org/10.1021/acsptsci.0c00196] [PMID: 33615182]

Offman, M.N.; Krol, M.; Patel, N.; Krishnan, S.; Liu, J.; Saha, V.; Bates, P.A. Rational engineering of L-asparaginase reveals importance of dual activity for cancer cell toxicity. Blood, 2011, 117(5), 1614-1621.
[http://dx.doi.org/10.1182/blood-2010-07-298422] [PMID: 21106986]

Covini, D.; Tardito, S.; Bussolati, O.; Chiarelli, L.R.; Pasquetto, M.V.; Digilio, R.; Valentini, G.; Scotti, C. Expanding targets for a metabolic therapy of cancer: L-asparaginase. Recent Patents Anticancer Drug Discov., 2012, 7(1), 4-13.
[http://dx.doi.org/10.2174/157489212798358001] [PMID: 21854356]

Nowak-Göttl, U.; Wolff, J.E.A.; Kuhn, N.; Boos, J.; Kehrel, B.; Lilienweiss, V.; Schwabe, D.; Jürgens, H. Enhanced thrombin generation, P-von willebrand factor, P-fibrin D-dimer and P-plasminogen activator inhibitor 1: Predictive for venous thrombosis in asparaginase-treated children. Fibrinolysis and Proteolysis, 1994, 8(2), 63-65.
[http://dx.doi.org/10.1016/0268-9499(94)90248-8]

Rizzari, C.; Zucchetti, M.; Conter, V.; Diomede, L.; Bruno, A.; Gavazzi, L.; Paganini, M.; Sparano, P.; Lo Nigro, L.; Aricò, M.; Milani, M.; D’Incalci, M. L-asparagine depletion and L-asparaginase activity in children with acute lymphoblastic leukemia receiving i.m. or i.v. Erwinia C. or E. coli L-asparaginase as first exposure. Ann. Oncol., 2000, 11(2), 189-193.
[http://dx.doi.org/10.1023/A:1008368916800] [PMID: 10761754]

Brumano, L.P.; da Silva, F.V.S.; Costa-Silva, T.A.; Apolinário, A.C.; Santos, J.H.P.M.; Kleingesinds, E.K.; Monteiro, G.; Rangel-Yagui, C.O.; Benyahia, B.; Junior, A.P. Development of L-asparaginase biobetters: Current research status and review of the desirable quality profiles. Front. Bioeng. Biotechnol., 2019, 6, 212.
[http://dx.doi.org/10.3389/fbioe.2018.00212] [PMID: 30687702]

Meneguetti, G.P.; Santos, J.H.P.M.; Obreque, K.M.T.; Barbosa, C.M.V.; Monteiro, G.; Farsky, S.H.P.; Marim de Oliveira, A.; Angeli, C.B.; Palmisano, G.; Ventura, S.P.M.; Pessoa-Junior, A.; de Oliveira Rangel-Yagui, C. Novel site-specific PEGylated L-asparaginase. PLoS One, 2019, 14(2), e0211951.
[http://dx.doi.org/10.1371/journal.pone.0211951] [PMID: 30753228]

Kotzia, G.A.; Lappa, K.; Labrou, N.E. Tailoring structure-function properties of L-asparaginase: engineering resistance to trypsin cleavage. Biochem. J., 2007, 404(2), 337-343.
[http://dx.doi.org/10.1042/BJ20061708] [PMID: 17313368]

Ardalan, N.; Mirzaie, S.; Sepahi, A.A.; Khavari-Nejad, R.A. Novel mutant of Escherichia coli asparaginase II to reduction of the glutaminase activity in treatment of acute lymphocytic leukemia by molecular dynamics simulations and QM-MM studies. Med. Hypotheses, 2018, 112, 7-17.
[http://dx.doi.org/10.1016/j.mehy.2018.01.004] [PMID: 29447943]

Chan, W.K.; Horvath, T.D.; Tan, L.; Link, T.; Harutyunyan, K.G.; Pontikos, M.A.; Anishkin, A.; Du, D.; Martin, L.A.; Yin, E.; Rempe, S.B.; Sukharev, S.; Konopleva, M.; Weinstein, J.N.; Lorenzi, P.L. Glutaminase activity of L-asparaginase contributes to durable preclinical activity against acute lymphoblastic leukemia. Mol. Cancer Ther., 2019, 18(9), 1587-1592.
[http://dx.doi.org/10.1158/1535-7163.MCT-18-1329] [PMID: 31209181]

Nguyen, H.A.; Su, Y.; Zhang, J.Y.; Antanasijevic, A.; Caffrey, M.; Schalk, A.M.; Liu, L.; Rondelli, D.; Oh, A.; Mahmud, D.L.; Bosland, M.C.; Kajdacsy-Balla, A.; Peirs, S.; Lammens, T.; Mondelaers, V.; De Moerloose, B.; Goossens, S.; Schlicht, M.J.; Kabirov, K.K.; Lyubimov, A.V.; Merrill, B.J.; Saunthararajah, Y.; Van Vlierberghe, P.; Lavie, A. A novel L-asparaginase with low L-glutaminase coactivity is highly efficacious against both T- and B-cell acute lymphoblastic leukemias in vivo. Cancer Res., 2018, 78(6), 1549-1560.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-2106] [PMID: 29343523]

Rodríguez-Martínez, J.A.; Rivera-Rivera, I.; Solá, R.J.; Griebenow, K. Enzymatic activity and thermal stability of PEG-α-chymotrypsin conjugates. Biotechnol. Lett., 2009, 31(6), 883-887.
[http://dx.doi.org/10.1007/s10529-009-9947-y] [PMID: 19224136]

Cho, Y.W.; Park, J.H.; Park, J.S.; Park, K. Pegylation: Camouflage of proteins, cells, and nanoparticles against recognition by the body’s defense mechanism. Pharmaceu-tical Sciences Encyclopedia; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2010, pp. 1-20.
[http://dx.doi.org/10.1002/9780470571224.pse303]

Ginn, C.; Khalili, H.; Lever, R.; Brocchini, S. PEGylation and its impact on the design of new protein-based medicines. Future Med. Chem., 2014, 6(16), 1829-1846.
[http://dx.doi.org/10.4155/fmc.14.125] [PMID: 25407370]

Swierczewska, M.; Lee, K.C.; Lee, S. What is the future of PEGylated therapies? Expert Opin. Emerg. Drugs, 2015, 20(4), 531-536.
[http://dx.doi.org/10.1517/14728214.2015.1113254] [PMID: 26583759]

Gupta, V.; Bhavanasi, S.; Quadir, M.; Singh, K.; Ghosh, G.; Vasamreddy, K.; Ghosh, A.; Siahaan, T.J.; Banerjee, S.; Banerjee, S.K. Protein PEGylation for cancer therapy: bench to bedside. J. Cell Commun. Signal., 2019, 13(3), 319-330.
[http://dx.doi.org/10.1007/s12079-018-0492-0] [PMID: 30499020]

Sindhu, R.; Pradeep, H.; Manonmani, H.K. Polyethylene glycol acts as a mechanistic stabilizer of L-asparaginase: A computational probing. Med. Chem., 2019, 15(6), 705-714.
[http://dx.doi.org/10.2174/1573406415666190206232816] [PMID: 30727907]

Fishburn, C.S. The pharmacology of PEGylation: balancing PD with PK to generate novel therapeutics. J. Pharm. Sci., 2008, 97(10), 4167-4183.
[http://dx.doi.org/10.1002/jps.21278] [PMID: 18200508]

Dinndorf, P.A.; Gootenberg, J.; Cohen, M.H.; Keegan, P.; Pazdur, R. FDA drug approval summary: pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Oncologist, 2007, 12(8), 991-998.
[http://dx.doi.org/10.1634/theoncologist.12-8-991] [PMID: 17766659]

Zalewska-Szewczyk, B.; Gach, A.; Wyka, K.; Bodalski, J. Młynarski, W. The cross-reactivity of anti-asparaginase antibodies against different L-asparaginase prepara-tions. Clin. Exp. Med., 2009, 9(2), 113-116.
[http://dx.doi.org/10.1007/s10238-008-0026-9] [PMID: 19184328]

Pui, C.H.; Liu, Y.; Relling, M.V. How to solve the problem of hypersensitivity to asparaginase? Pediatr. Blood Cancer, 2018, 65(3)
[http://dx.doi.org/10.1002/pbc.26884] [PMID: 29165928]

Lopes, A.M.; Oliveira-Nascimento, L.; Ribeiro, A.; Tairum, C.A., Jr; Breyer, C.A.; Oliveira, M.A.; Monteiro, G.; Souza-Motta, C.M.; Magalhães, P.O.; Avendaño, J.G.F.; Cavaco-Paulo, A.M.; Mazzola, P.G.; Rangel-Yagui, C.O.; Sette, L.D.; Converti, A.; Pessoa, A. Therapeutic l-asparaginase: upstream, downstream and beyond. Crit. Rev. Biotechnol., 2017, 37(1), 82-99.
[http://dx.doi.org/10.3109/07388551.2015.1120705] [PMID: 26694875]

Heitink-Pollé, K.M.J.; Prinsen, B.H.C.M.T.; de Koning, T.J.; van Hasselt, P.M.; Bierings, M.B. High incidence of symptomatic hyperammonemia in children with acute lymphoblastic leukemia receiving pegylated asparaginase.JIMD Reports; Springer, 2013, Vol. 7, pp. 103-108.
[http://dx.doi.org/10.1007/8904_2012_156]

Patra, J.K.; Das, G.; Fraceto, L.F.; Campos, E.V.R.; Rodriguez-Torres, M.D.P.; Acosta-Torres, L.S.; Diaz-Torres, L.A.; Grillo, R.; Swamy, M.K.; Sharma, S.; Habtemariam, S.; Shin, H.S. Nano based drug delivery systems: recent developments and future prospects. J. Nanobiotechnology, 2018, 16(1), 71.
[http://dx.doi.org/10.1186/s12951-018-0392-8] [PMID: 30231877]

Blanco, E.; Shen, H.; Ferrari, M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol., 2015, 33(9), 941-951.
[http://dx.doi.org/10.1038/nbt.3330] [PMID: 26348965]

Allen, T.M.; Cullis, P.R. Liposomal drug delivery systems: from concept to clinical applications. Adv. Drug Deliv. Rev., 2013, 65(1), 36-48.
[http://dx.doi.org/10.1016/j.addr.2012.09.037] [PMID: 23036225]

Hua, S.; Wu, S.Y.; Cabot, P.J.; Rakesh, G. The use of lipid-based nanocarriers for targeted pain therapies. Front. Pharmacol., 2013, 4, 143.
[http://dx.doi.org/10.3389/fphar.2013.00143] [PMID: 24319430]

Sercombe, L.; Veerati, T.; Moheimani, F.; Wu, S.Y.; Sood, A.K.; Hua, S. Advances and challenges of liposome assisted drug delivery. Front. Pharmacol., 2015, 6, 286.
[http://dx.doi.org/10.3389/fphar.2015.00286] [PMID: 26648870]

La-Beck, N.M.; Liu, X.; Wood, L.M. Harnessing liposome interactions with the immune system for the next breakthrough in cancer drug delivery. Front. Pharmacol., 2019, 10, 220.
[http://dx.doi.org/10.3389/fphar.2019.00220] [PMID: 30914953]

Ulrich, A.S. Biophysical aspects of using liposomes as delivery vehicles. Biosci. Rep., 2002, 22(2), 129-150.
[http://dx.doi.org/10.1023/A:1020178304031] [PMID: 12428898]

Moreira, J.N.; Gaspar, R.; Allen, T.M. Targeting stealth liposomes in a murine model of human small cell lung cancer. Biochim. Biophys. Acta, 2001, 1515(2), 167-176.
[http://dx.doi.org/10.1016/S0005-2736(01)00411-4] [PMID: 11718672]

Muro, S.; Muzykantov, V.R. Targeting of antioxidant and anti-thrombotic drugs to endothelial cell adhesion molecules. Curr. Pharm. Des., 2005, 11(18), 2383-2401.
[http://dx.doi.org/10.2174/1381612054367274] [PMID: 16022673]

Baran, E.T.; Ozer, N.; Hasirci, V. In vivo half life of nanoencapsulated L-asparaginase. J. Mater. Sci. Mater. Med., 2002, 13(12), 1113-1121.
[http://dx.doi.org/10.1023/A:1021125617828] [PMID: 15348652]

Bahreini, E.; Aghaiypour, K.; Abbasalipourkabir, R.; Mokarram, A.R.; Goodarzi, M.T.; Saidijam, M. Preparation and nanoencapsulation of l-asparaginase II in chitosan-tripolyphosphate nanoparticles and in vitro release study. Nanoscale Res. Lett., 2014, 9(1), 340.
[http://dx.doi.org/10.1186/1556-276X-9-340] [PMID: 25114635]

Blackman, L.D.; Varlas, S.; Arno, M.C.; Houston, Z.H.; Fletcher, N.L.; Thurecht, K.J.; Hasan, M.; Gibson, M.I.; O’Reilly, R.K. Confinement of therapeutic enzymes in selectively permeable polymer vesicles by Polymerization-Induced Self-Assembly (PISA) reduces antibody binding and proteolytic susceptibility. ACS Cent. Sci., 2018, 4(6), 718-723.
[http://dx.doi.org/10.1021/acscentsci.8b00168] [PMID: 29974067]

Domenech, C.; Thomas, X.; Chabaud, S.; Baruchel, A.; Gueyffier, F.; Mazingue, F.; Auvrignon, A.; Corm, S.; Dombret, H.; Chevallier, P.; Galambrun, C.; Huguet, F.; Legrand, F.; Mechinaud, F.; Vey, N.; Philip, I.; Liens, D.; Godfrin, Y.; Rigal, D.; Bertrand, Y. l-asparaginase loaded red blood cells in refractory or relapsing acute lym-phoblastic leukaemia in children and adults: results of the GRASPALL 2005-01 randomized trial. Br. J. Haematol., 2011, 153(1), 58-65.
[http://dx.doi.org/10.1111/j.1365-2141.2011.08588.x] [PMID: 21332712]

Hunault-Berger, M.; Leguay, T.; Huguet, F.; Leprêtre, S.; Deconinck, E.; Ojeda-Uribe, M.; Bonmati, C.; Escoffre-Barbe, M.; Bories, P.; Himberlin, C.; Chevallier, P.; Rousselot, P.; Reman, O.; Boulland, M-L.; Lissandre, S.; Turlure, P.; Bouscary, D.; Sanhes, L.; Legrand, O.; Lafage-Pochitaloff, M.; Béné, M.C.; Liens, D.; Godfrin, Y.; Ifrah, N.; Dombret, H. Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). A Phase 2 study of L-asparaginase encapsulated in erythrocytes in el-derly patients with Philadelphia chromosome negative acute lymphoblastic leukemia: The GRASPALL/GRAALL-SA2-2008 study. Am. J. Hematol., 2015, 90(9), 811-818.
[http://dx.doi.org/10.1002/ajh.24093] [PMID: 26094614]

Bertrand, Y.; Baruchel, A.; Thomas, X.G.; Blin, N.; Tardy, E.T.; Perel, Y.; Vey, N.; Gandemer, V.; Cacheux, V.; Mazingue, F.; Raffoux, E.; Plat, G.; Poiree, M.; Stephan, J-L.; Auvrignon, A.; Plantaz, D.; Pellier, I.; Bonin, C.; El-Hariry, I.; Ferster, A. Clinical activity of ERY001 (Erythrocyte encapsulated L-asparaginase) and native L-asparaginase (L-ASP) in combination with COOPRALL regimen in Phase III randomized trial in patients with relapsed Acute Lymphoblastic Leukemia (ALL). J. Clin. Oncol., 2015, 33, 7004-7004.
[http://dx.doi.org/10.1200/jco.2015.33.15_suppl.7004]

Thomas, X.G.; Tardy, E.T.; Guieze, R.; Chevallier, P.; Marolleau, J. pierre; Orsini, F.; Hitchcock, I.; El-Hariry, I. GRASPA-AML 2012-01 Study (NCT01810705): A multicenter, open, randomized Phase 2b trial evaluating ERY001 (L-asparaginase encapsulated in Red Blood Cells) plus low-dose cytarabine vs low-dose cytarabine alone, in treatment of newly diagnosed Acute Myeloid Leukemia (AML) elderly patients, unfit for intensive chemotherapy. J. Clin. Oncol., 2015, 33.
[http://dx.doi.org/10.1200/jco.2015.33.15_suppl.tps7099]

Keck, C.M.; Müller, R.H. Nanotoxicological classification system (NCS) - a guide for the risk-benefit assessment of nanoparticulate drug delivery systems. Eur. J. Pharm. Biopharm., 2013, 84(3), 445-448.
[http://dx.doi.org/10.1016/j.ejpb.2013.01.001] [PMID: 23333302]

Wicki, A.; Witzigmann, D.; Balasubramanian, V.; Huwyler, J. Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications. J. Control. Release, 2015, 200, 138-157.
[http://dx.doi.org/10.1016/j.jconrel.2014.12.030] [PMID: 25545217]

Matsumura, Y.; Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the anti-tumor agent smancs. Cancer Res., 1986, 46(12 Pt 1), 6387-6392.
[PMID: 2946403]

Prabhakar, U.; Maeda, H.; Jain, R.K.; Sevick-Muraca, E.M.; Zamboni, W.; Farokhzad, O.C.; Barry, S.T.; Gabizon, A.; Grodzinski, P.; Blakey, D.C. Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology. Cancer Res., 2013, 73(8), 2412-2417.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-4561] [PMID: 23423979]

Tanaka, N.; Kanatani, S.; Tomer, R.; Sahlgren, C.; Kronqvist, P.; Kaczynska, D.; Louhivuori, L.; Kis, L.; Lindh, C.; Mitura, P.; Stepulak, A.; Corvigno, S.; Hartman, J.; Micke, P.; Mezheyeuski, A.; Strell, C.; Carlson, J.W.; Fernández Moro, C.; Dahlstrand, H.; Östman, A.; Matsumoto, K.; Wiklund, P.; Oya, M.; Miyakawa, A.; Deisseroth, K.; Uhlén, P. Whole-tissue biopsy phenotyping of three-dimensional tumours reveals patterns of cancer heterogeneity. Nat. Biomed. Eng., 2017, 1(10), 796-806.
[http://dx.doi.org/10.1038/s41551-017-0139-0] [PMID: 31015588]

Golombek, S.K.; May, J.N.; Theek, B.; Appold, L.; Drude, N.; Kiessling, F.; Lammers, T. Tumor targeting via EPR: Strategies to enhance patient responses. Adv. Drug Deliv. Rev., 2018, 130, 17-38.
[http://dx.doi.org/10.1016/j.addr.2018.07.007] [PMID: 30009886]

Cruz, M.E.M.; Gaspar, M.M.; Lopes, F.; Jorge, J.S.; Perez-Soler, R. Liposomal L-asparaginase: in vitro evaluation. Int. J. Pharm., 1993, 96(1-3), 67-77.
[http://dx.doi.org/10.1016/0378-5173(93)90213-Y]

Gasper, M.M.; Blanco, D.; Cruz, M.E.M.; Alonso, M.J. Formulation of L-asparaginase-loaded poly(lactide-co-glycolide) nanoparticles: influence of polymer properties on enzyme loading, activity and in vitro release. J. Control. Release, 1998, 52(1-2), 53-62.
[http://dx.doi.org/10.1016/S0168-3659(97)00196-X] [PMID: 9685935]

Wolf, M.; Wirth, M.; Pittner, F.; Gabor, F. Stabilisation and determination of the biological activity of L-asparaginase in poly(D,L-lactide-co-glycolide) nanospheres. Int. J. Pharm., 2003, 256(1-2), 141-152.
[http://dx.doi.org/10.1016/S0378-5173(03)00071-1] [PMID: 12695020]

Zhang, Y-Q.; Tao, M-L.; Shen, W-D.; Zhou, Y-Z.; Ding, Y.; Ma, Y.; Zhou, W-L. Immobilization of L-asparaginase on the microparticles of the natural silk sericin protein and its characters. Biomaterials, 2004, 25(17), 3751-3759.
[http://dx.doi.org/10.1016/j.biomaterials.2003.10.019] [PMID: 15020151]

Godfrin, Y.; Thomas, X.; Bertrand, Y.; Duget, C. L-asparaginase loaded into erythrocytes (GRASPA): Principle and interests in acute lymphoblastic leukemia. Blood, 2007, 110(11), 4325-4325.
[http://dx.doi.org/10.1182/blood.V110.11.4325.4325]

De, A.; Venkatesh, D.N.; Nagaswamy, D. Design and evaluation of liposomal delivery system for L-asparaginese. J. Appl. Pharm. Sci., 2012, (08), 112-117.
[http://dx.doi.org/10.7324/JAPS.2012.2818]

Wan, S.; He, D.; Yuan, Y.; Yan, Z.; Zhang, X.; Zhang, J. Chitosan-modified lipid nanovesicles for efficient systemic delivery of l-asparaginase. Colloids Surf. B Biointerfaces, 2016, 143, 278-284.
[http://dx.doi.org/10.1016/j.colsurfb.2016.03.046] [PMID: 27022867]

Sueyoshi, D.; Anraku, Y.; Komatsu, T.; Urano, Y.; Kataoka, K. Enzyme-loaded polyion complex vesicles as in vivo nanoreactors working sustainably under the blood circulation: characterization and functional evaluation. Biomacromolecules, 2017, 18(4), 1189-1196.
[http://dx.doi.org/10.1021/acs.biomac.6b01870] [PMID: 28233988]

Apolinário, A.C. Magoń, M.S.; Pessoa, A., Jr; Rangel-Yagui, C.de.O. Challenges for the self-assembly of poly(Ethylene glycol)-poly(lactic acid) (PEG-PLA) into poly-mersomes: Beyond the theoretical paradigms. Nanomaterials (Basel), 2018, 8(6), E373.
[http://dx.doi.org/10.3390/nano8060373] [PMID: 29861449]

Hammel, P.; Fabienne, P.; Mineur, L.; Metges, J.P.; Andre, T.; De La Fouchardiere, C.; Louvet, C.; El Hajbi, F.; Faroux, R.; Guimbaud, R.; Tougeron, D.; Bouche, O.; Lecomte, T.; Rebischung, C.; Tournigand, C.; Cros, J.; Kay, R.; Hamm, A.; Gupta, A.; Bachet, J.B.; El Hariry, I. Erythrocyte-encapsulated asparaginase (eryaspase) com-bined with chemotherapy in second-line treatment of advanced pancreatic cancer: An open-label, randomized Phase IIb trial. Eur. J. Cancer, 2020, 124, 91-101.
[http://dx.doi.org/10.1016/j.ejca.2019.10.020] [PMID: 31760314]

Singh, M.; Hassan, N.; Verma, D.; Thakur, P.; Panda, B.P.; Panda, A.K.; Sharma, R.K.; Mirza, A.; Mansoor, S.; Alrokayan, S.H.; Khan, H.A.; Ahmad, P.; Iqbal, Z. Design of expert guided investigation of native L-asparaginase encapsulated long-acting cross-linker-free poly (lactic-co-glycolic) acid nanoformulation in an Ehrlich ascites tu-mor model. Saudi Pharm. J., 2020, 28(6), 719-728.
[http://dx.doi.org/10.1016/j.jsps.2020.04.014] [PMID: 32550804]

Sedighi, M.; Zahedi Bialvaei, A.; Hamblin, M. R.; Ohadi, E.; Asadi, A.; Halajzadeh, M.; Lohrasbi, V.; Mohammadzadeh, N.; Amiriani, T.; Krutova, M.; Amini, A.; Kouhsari, E. Therapeutic bacteria to combat cancer; current advances, challenges, and opportunities. Cancer Med., 2019, 8(6), cam4.2148.
[http://dx.doi.org/10.1002/cam4.2148]

Graham, F.O.; Coleman, P.N. Infection of a secondary carcinoma by Salmonella montevideo. BMJ, 1952, 1(4768), 1116.
[http://dx.doi.org/10.1136/bmj.1.4768.1116] [PMID: 14925388]

Gill, G.V.; Holden, A. A malignant pleural effusion infected with Salmonella enteritidis. Thorax, 1996, 51(1), 104-105.
[http://dx.doi.org/10.1136/thx.51.1.104] [PMID: 8658357]

Pawelek, J.M.; Low, K.B.; Bermudes, D. Bacteria as tumour-targeting vectors. Lancet Oncol., 2003, 4(9), 548-556.
[http://dx.doi.org/10.1016/S1470-2045(03)01194-X] [PMID: 12965276]

Toso, J.F.; Gill, V.J.; Hwu, P.; Marincola, F.M.; Restifo, N.P.; Schwartzentruber, D.J.; Sherry, R.M.; Topalian, S.L.; Yang, J.C.; Stock, F.; Freezer, L.J.; Morton, K.E.; Seipp, C.; Haworth, L.; Mavroukakis, S.; White, D.; MacDonald, S.; Mao, J.; Sznol, M.; Rosenberg, S.A.; Phase, I. Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma. J. Clin. Oncol., 2002, 20(1), 142-152.
[http://dx.doi.org/10.1200/JCO.2002.20.1.142] [PMID: 11773163]

Thamm, D.H.; Kurzman, I.D.; King, I.; Li, Z.; Sznol, M.; Dubielzig, R.R.; Vail, D.M.; MacEwen, E.G. Systemic administration of an attenuated, tumor-targeting Salmonel-la typhimurium to dogs with spontaneous neoplasia: phase I evaluation. Clin. Cancer Res., 2005, 11(13), 4827-4834.
[http://dx.doi.org/10.1158/1078-0432.CCR-04-2510] [PMID: 16000580]

Zhou, S.; Gravekamp, C.; Bermudes, D.; Liu, K. Tumour-targeting bacteria engineered to fight cancer. Nat. Rev. Cancer, 2018, 18(12), 727-743.
[http://dx.doi.org/10.1038/s41568-018-0070-z] [PMID: 30405213]

Forbes, N.S. Engineering the perfect (bacterial) cancer therapy. Nat. Rev. Cancer, 2010, 10(11), 785-794.
[http://dx.doi.org/10.1038/nrc2934] [PMID: 20944664]

Broadway, K.M.; Scharf, B.E. Salmonella typhimurium as an anticancer therapy: Recent advances and perspectives. Curr. Clin. Microbiol. Rep., 2019, 6, 225-239.
[http://dx.doi.org/10.1007/s40588-019-00132-5]

Eisenstark, A.; Kazmierczak, R.A.; Dino, A.; Khreis, R.; Newman, D.; Schatten, H. Development of Salmonella strains as cancer therapy agents and testing in tumor cell lines. Methods Mol. Biol., 2007, 394, 323-354.
[http://dx.doi.org/10.1007/978-1-59745-512-1_16] [PMID: 18363243]

Kim, K.; Jeong, J.H.; Lim, D.; Hong, Y.; Lim, H-J.; Kim, G-J.; Shin, S-R.; Lee, J-J.; Yun, M.; Harris, R.A.; Min, J-J.; Choy, H.E. L-Asparaginase delivered by Salmonella typhimurium suppresses solid tumors. Mol. Ther. Oncolytics, 2015, 2, 15007.
[http://dx.doi.org/10.1038/mto.2015.7] [PMID: 27119104]

Kim, K.; Min, S.Y.; Lim, H.D.; You, S.H.; Lim, D.; Jeong, J.H.; Kim, H.J.; Rhee, J.H.; Park, K.; Shin, M.; Kim, G.J.; Min, J.J.; Choy, H.E. Cell mass-dependent expression of an anticancer protein drug by tumor-targeted Salmonella. Oncotarget, 2018, 9(9), 8548-8559.
[http://dx.doi.org/10.18632/oncotarget.24013] [PMID: 29492216]

Nguyen, V.H.; Kim, H.S.; Ha, J.M.; Hong, Y.; Choy, H.E.; Min, J.J. Genetically engineered Salmonella typhimurium as an imageable therapeutic probe for cancer. Cancer Res., 2010, 70(1), 18-23.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-3453] [PMID: 20028866]

Jiang, S.N.; Park, S.H.; Lee, H.J.; Zheng, J.H.; Kim, H.S.; Bom, H.S.; Hong, Y.; Szardenings, M.; Shin, M.G.; Kim, S.C.; Ntziachristos, V.; Choy, H.E.; Min, J.J. Engineering of bacteria for the visualization of targeted delivery of a cytolytic anticancer agent. Mol. Ther., 2013, 21(11), 1985-1995.
[http://dx.doi.org/10.1038/mt.2013.183] [PMID: 23922014]

Crull, K.; Bumann, D.; Weiss, S. Influence of infection route and virulence factors on colonization of solid tumors by Salmonella enterica serovar Typhimurium. FEMS Immunol. Med. Microbiol., 2011, 62(1), 75-83.
[http://dx.doi.org/10.1111/j.1574-695X.2011.00790.x] [PMID: 21314734]

Felgner, S.; Kocijancic, D.; Frahm, M.; Heise, U.; Rohde, M.; Zimmermann, K.; Falk, C.; Erhardt, M.; Weiss, S. Engineered Salmonella enterica serovar Typhimurium overcomes limitations of anti-bacterial immunity in bacteria-mediated tumor therapy. OncoImmunology, 2017, 7(2), e1382791.
[http://dx.doi.org/10.1080/2162402X.2017.1382791] [PMID: 29308303]

Abaji, R.; Krajinovic, M. Pharmacogenetics of asparaginase in acute lymphoblastic leukemia. Cancer Drug Resist., 2019, 2(2), 242-255.
[http://dx.doi.org/10.20517/cdr.2018.24]

De Morais, S.B.; De Souza, T.D.A.C.B. Human L-asparaginase: Acquiring knowledge of its activation. Int. J. Oncol., 2021, 58(4), 1-13. [Review].
[http://dx.doi.org/10.3892/ijo.2021.5191] [PMID: 33649821]

Derst, C.; Henseling, J.; Röhm, K.H. Engineering the substrate specificity of Escherichia coli asparaginase. II. Selective reduction of glutaminase activity by amino acid replacements at position 248. Protein Sci., 2000, 9(10), 2009-2017.
[http://dx.doi.org/10.1110/ps.9.10.2009] [PMID: 11106175]

Emadi, A.; Law, J.Y.; Strovel, E.T.; Lapidus, R.G.; Jeng, L.J.B.; Lee, M.; Blitzer, M.G.; Carter-Cooper, B.A.; Sewell, D.; Van Der Merwe, I.; Philip, S.; Imran, M.; Yu, S.L.; Li, H.; Amrein, P.C.; Duong, V.H.; Sausville, E.A.; Baer, M.R.; Fathi, A.T.; Singh, Z.; Bentzen, S.M. Asparaginase Erwinia chrysanthemi effectively depletes plasma glu-tamine in adult patients with relapsed/refractory acute myeloid leukemia. Cancer Chemother. Pharmacol., 2018, 81(1), 217-222.
[http://dx.doi.org/10.1007/s00280-017-3459-6] [PMID: 29119293]

Parmentier, J.H.; Maggi, M.; Tarasco, E.; Scotti, C.; Avramis, V.I.; Mittelman, S.D. Glutaminase activity determines cytotoxicity of L-asparaginases on most leukemia cell lines. Leuk. Res., 2015, 39(7), 757-762.
[http://dx.doi.org/10.1016/j.leukres.2015.04.008] [PMID: 25941002]

Souba, W.W. Glutamine and cancer. Ann. Surg., 1993, 218(6), 715-728.
[http://dx.doi.org/10.1097/00000658-199312000-00004] [PMID: 8257221]

Chen, L.; Cui, H. Targeting glutamine induces apoptosis: A cancer therapy approach. Int. J. Mol. Sci., 2015, 16(9), 22830-22855.
[http://dx.doi.org/10.3390/ijms160922830] [PMID: 26402672]

Valter, K.; Chen, L.; Kruspig, B.; Maximchik, P.; Cui, H.; Zhivotovsky, B.; Gogvadze, V. Contrasting effects of glutamine deprivation on apoptosis induced by conven-tionally used anticancer drugs. Biochim. Biophys. Acta Mol. Cell Res., 2017, 1864(3), 498-506.
[http://dx.doi.org/10.1016/j.bbamcr.2016.12.016] [PMID: 27993669]

Zhang, J.; Fan, J.; Venneti, S.; Cross, J.R.; Takagi, T.; Bhinder, B.; Djaballah, H.; Kanai, M.; Cheng, E.H.; Judkins, A.R.; Pawel, B.; Baggs, J.; Cherry, S.; Rabinowitz, J.D.; Thompson, C.B. Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion. Mol. Cell, 2014, 56(2), 205-218.
[http://dx.doi.org/10.1016/j.molcel.2014.08.018] [PMID: 25242145]

Chan, W.K.; Lorenzi, P.L.; Anishkin, A.; Purwaha, P.; Rogers, D.M.; Sukharev, S.; Rempe, S.B.; Weinstein, J.N. The glutaminase activity of L-asparaginase is not required for anticancer activity against ASNS-negative cells. Blood, 2014, 123(23), 3596-3606.
[http://dx.doi.org/10.1182/blood-2013-10-535112] [PMID: 24659632]

Panosyan, E.H.; Grigoryan, R.S.; Avramis, I.A.; Seibel, N.L.; Gaynon, P.S.; Siegel, S.E.; Fingert, H.J.; Avramis, V.I. Deamination of glutamine is a prerequisite for optimal asparagine deamination by asparaginases in vivo (CCG-1961). Anticancer Res., 2004, 24(2C), 1121-1125.
[PMID: 15154634]

Jiang, J.; Pavlova, N.N.; Zhang, J. Asparagine, a critical limiting metabolite during glutamine starvation. Mol. Cell. Oncol., 2018, 5(3), e1441633.
[http://dx.doi.org/10.1080/23723556.2018.1441633] [PMID: 30250896]

Klionsky, D.J.; Cuervo, A.M.; Dunn, W.A., Jr; Levine, B.; van der Klei, I.; Seglen, P.O. How shall I eat thee? Autophagy, 2007, 3(5), 413-416.
[http://dx.doi.org/10.4161/auto.4377] [PMID: 17568180]

Mei, Y.; Thompson, M.D.; Cohen, R.A.; Tong, X. Autophagy and oxidative stress in cardiovascular diseases. Biochim. Biophys. Acta, 2015, 1852(2), 243-251.
[http://dx.doi.org/10.1016/j.bbadis.2014.05.005] [PMID: 24834848]

Jia, G.; Sowers, J.R. Autophagy: a housekeeper in cardiorenal metabolic health and disease. Biochim. Biophys. Acta, 2015, 1852(2), 219-224.
[http://dx.doi.org/10.1016/j.bbadis.2014.06.025] [PMID: 24984281]

Evangelisti, C.; Evangelisti, C.; Chiarini, F.; Lonetti, A.; Buontempo, F.; Neri, L.M.; McCubrey, J.A.; Martelli, A.M. Autophagy in acute leukemias: a double-edged sword with important therapeutic implications. Biochim. Biophys. Acta, 2015, 1853(1), 14-26.
[http://dx.doi.org/10.1016/j.bbamcr.2014.09.023] [PMID: 25284725]

Li, X.; Xu, H.L.; Liu, Y.X.; An, N.; Zhao, S.; Bao, J.K. Autophagy modulation as a target for anticancer drug discovery. Acta Pharmacol. Sin., 2013, 34(5), 612-624.
[http://dx.doi.org/10.1038/aps.2013.23] [PMID: 23564085]

Zhang, S.P.; Niu, Y.N.; Yuan, N.; Zhang, A.H.; Chao, D.; Xu, Q.P.; Wang, L.J.; Zhang, X.G.; Zhao, W.L.; Zhao, Y.; Wang, J.R. Role of autophagy in acute myeloid leukemia therapy. Chin. J. Cancer, 2013, 32(3), 130-135.
[http://dx.doi.org/10.5732/cjc.012.10073] [PMID: 22854065]

Auberger, P.; Puissant, A. Autophagy, a key mechanism of oncogenesis and resistance in leukemia. Blood, 2017, 129(5), 547-552.
[http://dx.doi.org/10.1182/blood-2016-07-692707] [PMID: 27956388]

Song, P.; Ye, L.; Fan, J.; Li, Y.; Zeng, X.; Wang, Z.; Wang, S.; Zhang, G.; Yang, P.; Cao, Z.; Ju, D. Asparaginase induces apoptosis and cytoprotective autophagy in chronic myeloid leukemia cells. Oncotarget, 2015, 6(6), 3861-3873.
[http://dx.doi.org/10.18632/oncotarget.2869] [PMID: 25738356]

Takahashi, H.; Inoue, J.; Sakaguchi, K.; Takagi, M.; Mizutani, S.; Inazawa, J. Autophagy is required for cell survival under L-asparaginase-induced metabolic stress in acute lymphoblastic leukemia cells. Oncogene, 2017, 36(30), 4267-4276.
[http://dx.doi.org/10.1038/onc.2017.59] [PMID: 28346428]

Yu, M.; Henning, R.; Walker, A.; Kim, G.; Perroy, A.; Alessandro, R.; Virador, V.; Kohn, E.C. L-asparaginase inhibits invasive and angiogenic activity and induces autophagy in ovarian cancer. J. Cell. Mol. Med., 2012, 16(10), 2369-2378.
[http://dx.doi.org/10.1111/j.1582-4934.2012.01547.x] [PMID: 22333033]

Lorenzi, P.L.; Claerhout, S.; Mills, G.B.; Weinstein, J.N. A curated census of autophagy-modulating proteins and small molecules: candidate targets for cancer therapy. Autophagy, 2014, 10(7), 1316-1326.
[http://dx.doi.org/10.4161/auto.28773] [PMID: 24906121]

Polak, R.; Bierings, M.B.; van der Leije, C.S.; Sanders, M.A.; Roovers, O.; Marchante, J.R.M.; Boer, J.M.; Cornelissen, J.J.; Pieters, R.; den Boer, M.L.; Buitenhuis, M. Autophagy inhibition as a potential future targeted therapy for ETV6-RUNX1-driven B-cell precursor acute lymphoblastic leukemia. Haematologica, 2019, 104(4), 738-748.
[http://dx.doi.org/10.3324/haematol.2018.193631] [PMID: 30381299]

Takahashi, H.; Inoue, J.; Sakaguchi, K.; Takagi, M.; Mizutani, S.; Inazawa, J. Autophagy inhibition sensitizes acute lymphoblastic leukemia cells to L-asparaginase. Blood, 2015, 126(23), 3772-3772.
[http://dx.doi.org/10.1182/blood.V126.23.3772.3772]

Chen, Q.; Ye, L.; Fan, J.; Zhang, X.; Wang, H.; Liao, S.; Song, P.; Wang, Z.; Wang, S.; Li, Y.; Luan, J.; Wang, Y.; Chen, W.; Zai, W.; Yang, P.; Cao, Z.; Ju, D. Autophagy suppression potentiates the anti-glioblastoma effect of asparaginase in vitro and in vivo. Oncotarget, 2017, 8(53), 91052-91066.
[http://dx.doi.org/10.18632/oncotarget.19409] [PMID: 29207624]

Knott, S.R.V.; Wagenblast, E.; Khan, S.; Kim, S.Y.; Soto, M.; Wagner, M.; Turgeon, M-O.; Fish, L.; Erard, N.; Gable, A.L.; Maceli, A.R.; Dickopf, S.; Papachristou, E.K.; D’Santos, C.S.; Carey, L.A.; Wilkinson, J.E.; Harrell, J.C.; Perou, C.M.; Goodarzi, H.; Poulogiannis, G.; Hannon, G.J. Asparagine bioavailability governs metastasis in a model of breast cancer. Nature, 2018, 554(7692), 378-381.
[http://dx.doi.org/10.1038/nature25465] [PMID: 29414946]