Pegylated arginine deiminase treatment of patients with metastatic melanoma: results from phase I and II studies
Abstract
Purpose: Individuals with metastatic melanoma have a poor prognosis. Many human melanomas are auxotrophic for arginine, and arginine is not an essential amino acid in humans. We hypothesized that this auxotrophy may be therapeutically exploited. A novel amino acid–degrading enzyme (arginine deiminase) conjugated to polyethylene glycol (ADI-SS PEG 20,000 mw) was used to lower plasma arginine in individuals with metastatic melanoma. Patients and Methods: Two cohort dose-escalation studies were performed. A phase I study in the United States enrolled 15 patients, and a phase I to II study in Italy enrolled 24 patients. The Italian patients also received two subsequent cycles of treatment, each consisting of four once-weekly injections of 160 U/m 2. The goals of these studies were to determine pharmacokinetics (PK), pharmacodynamics (PD), safety, and the antitumor activity of ADI-SS PEG 20,000 mw. Results: PK and PD studies indicated that a dose of 160 U/m 2 lowered plasma arginine from a resting level of approximately 130 μmol/L to less than 2 μmol/L for at least 7 days; nitric oxide levels also were lowered. There were no grade 3 or 4 toxicities directly attributable to the drug. Six of 24 phase I to II patients responded to treatment (five partial responses and one complete response; 25% response rate) and also had prolonged survival. Conclusion: Elimination of all detectable plasma arginine in patients with metastatic melanoma was well tolerated and may be effective in the treatment of this cancer. Further testing of ADI-SS PEG 20,000 mw in a larger population of individuals with metastatic melanoma is warranted.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Recombinant pegylated arginine deiminase (ADI-PEG20) has been tested in clinical trials for melanoma and hepatocellular carcinoma with some therapeutic benefit.
“Recombinant pegylated arginine deiminase (ADI-PEG20) has been tested in clinical trials to treat melanoma and hepatocellular carcinoma with some therapeutic benefit (Ascierto et al., 2005; Izzo et al., 2004; Ott et al., 2013; Szlosarek et al., 2013; Yang et al., 2010).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Ascierto et al., 2005
Cites
Optimal two-stage designs for phase II clinical trials.
Simon, R. (1989) · Controlled Clinical Trials · doi:10.1016/0197-2456(89)90015-9 · Cited by 3,636 · see citing works
Final Version of the American Joint Committee on Cancer Staging System for Cutaneous Melanoma
Balch, C. M., Buzaid, A. C., Soong, S., Atkins, M. B., Cascinelli, N., Coit, D. G., Fleming, I. D., Gershenwald, J. E., Houghton, A. N., Kirkwood, J. M., et al. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.16.3635 · Cited by 2,627 · see citing works
iNOS-mediated nitric oxide production and its regulation
Aktan, F. (2004) · Life Sciences · doi:10.1016/j.lfs.2003.10.042 · Cited by 1,364 · see citing works
Management of Cutaneous Melanoma
Tsao, H., Atkins, M. B., & Sober, A. J. (2004) · New England Journal of Medicine · doi:10.1056/nejmra041245 · Cited by 857 · see citing works
Histone Deimination Antagonizes Arginine Methylation
Cuthbert, G. L., Daujat, S., Snowden, A. W., Erdjument‐Bromage, H., Hagiwara, T., Yamada, M., Schneider, R., Gregory, P. D., Tempst, P., Bannister, A. J., et al. (2004) · Cell · doi:10.1016/j.cell.2004.08.020 · Cited by 840 · see citing works
Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma
Lens, M. B., & Dawes, M. G. (2004) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2004.05708.x · Cited by 570 · see citing works
Kirkwood, J. M., Manola, J. B., Ibrahim, J. G., Sondak, V. K., Ernstoff, M. S., & Rao, U. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-1103-3 · Cited by 550 · see citing works
Re-evaluating the role of dacarbazine in metastatic melanoma: what have we learned in 30 years?
Eggermont, A. M. M., & Kirkwood, J. M. (2004) · European Journal of Cancer · doi:10.1016/j.ejca.2004.04.030 · Cited by 384 · see citing works
de Vries, E., Bray, F., Coebergh, J. W. W., Parkin, D. M., & European Network of Cancer Registries (2003) · International Journal of Cancer · doi:10.1002/ijc.11360 · Cited by 377 · see citing works
Regulation of Nitric Oxide Production by Arginine Metabolic Enzymes
Mori, M., & Gotoh, T. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3169 · Cited by 346 · see citing works
Argininosuccinate synthetase from the urea cycle to the citrulline–NO cycle
Husson, A., Brasse‐Lagnel, C., Fairand, A., Renouf, S., & Lavoinne, A. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03559.x · Cited by 329 · see citing works
Eigentler, T., Caroli, U. M., Radny, P., & Garbe, C. (2003) · The Lancet Oncology · doi:10.1016/s1470-2045(03)01280-4 · Cited by 323 · see citing works
Incidence and distribution of argininosuccinate synthetase deficiency in human cancers
Dillon, B. J., Prieto, V. G., Curley, S. A., Ensor, M., Holtsberg, F. W., Bomalaski, J. S., & Clark, M. A. (2004) · Cancer · doi:10.1002/cncr.20057 · Cited by 317 · see citing works
Self-citationEnsor, M., Holtsberg, F. W., Bomalaski, J. S., & Clark, M. A. (2002) · PubMed · Cited by 315 · see citing works
Self-citationIzzo, F., Marra, P., Beneduce, G., Castello, G., Vallone, P., De Rosa, V., Cremona, F., Ensor, C. M., Holtsberg, F. W., Bomalaski, J. S., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.11.120 · Cited by 250 · see citing works
Self-citationTapiero, H., Mathé, G., Couvreur, P., & Tew, K. D. (2002) · Biomedicine & Pharmacotherapy · doi:10.1016/s0753-3322(02)00284-6 · Cited by 249 · see citing works
Cancer immunotherapy: The interferon-α experience
Kirkwood, J. M. (2002) · Seminars in Oncology · doi:10.1053/sonc.2002.33078 · Cited by 213 · see citing works
Holtsberg, F. W., Ensor, M., Steiner, M. R., Bomalaski, J. S., & Clark, M. A. (2002) · Journal of Controlled Release · doi:10.1016/s0168-3659(02)00042-1 · Cited by 155 · see citing works
Self-citationNew TNM melanoma staging system: Linking biology and natural history to clinical outcomes
Balch, C. M., Buzaid, A. C., Soong, S., Atkins, M. B., Cascinelli, N., Coit, D. G., Fleming, I. D., Gershenwald, J. E., Houghton, A. N., Kirkwood, J. M., et al. (2003) · Seminars in Surgical Oncology · doi:10.1002/ssu.10020 · Cited by 124 · see citing works
In vivo anti‐tumor activity of arginine deiminase purified from Mycoplasma arginini
Takaku, H., Takase, M., Abe, S., Hayashi, H., & Miyazaki, K. (1992) · International Journal of Cancer · doi:10.1002/ijc.2910510213 · Cited by 123 · see citing works
Clinical Trial Designs for the Early Clinical Development of Therapeutic Cancer Vaccines
Simon, R. M., Steinberg, S. M., Hamilton, M., Hildesheim, A., Khleif, S. N., Kwak, L. W., Mackall, C. L., Schlom, J., Topalian, S. L., & Berzofsky, J. A. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.6.1848 · Cited by 113 · see citing works
Systemic chemotherapy in the treatment of malignant melanoma
Lens, M. B., & Eisen, T. G. (2003) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.4.12.2205 · Cited by 98 · see citing works
Antiapoptotic role of endogenous nitric oxide in human melanoma cells.
Salvucci, O., Carsana, M., Bersani, I., Tragni, G., & Anichini, A. (2001) · PubMed · Cited by 97 · see citing works
Arginine deiminase: a potential inhibitor of angiogenesis and tumour growth
Is, P., Kang, S.-W., Shin, Y.-J., Chae, K.-Y., Park, M.-O., Kim, M. Y., Wheatley, D. N., & Min, B.-H. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6601181 · Cited by 95 · see citing works
Takaku, H., Matsumoto, M., Misawa, S., & Miyazaki, K. (1995) · Japanese Journal of Cancer Research · doi:10.1111/j.1349-7006.1995.tb03094.x · Cited by 89 · see citing works
Sugimura, K., Ohno, T., Kusuyama, T., & Azuma, I. (1992) · Melanoma Research · doi:10.1097/00008390-199209000-00007 · Cited by 83 · see citing works
Arginine Deiminase Inhibits Cell Proliferation by Arresting Cell Cycle and Inducing Apoptosis
Gong, H., Zölzer, F., Recklinghausen, G. V., Rössler, J. K., Breit, S., Havers, W., Fotsis, T., & Schweigerer, L. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1004 · Cited by 76 · see citing works
Wheatley, D. N. (2004) · Anti-Cancer Drugs · doi:10.1097/00001813-200410000-00002 · Cited by 74 · see citing works
Role of Nitric Oxide in Tumor Angiogenesis
Morbidelli, L., Donnini, S., & Ziche, M. (2004) · Cancer treatment and research · doi:10.1007/978-1-4419-8871-3_11 · Cited by 70 · see citing works
Gonzalez, G., & Byus, C. V. (1991) · PubMed · Cited by 69 · see citing works
Depletion of Dietary Arginine Inhibits Growth of Metastatic Tumor
Yeatman, T. J. (1991) · Archives of Surgery · doi:10.1001/archsurg.1991.01410350066010 · Cited by 67 · see citing works
Dillon, B. J., Holtsberg, F. W., Ensor, M., Bomalaski, J. S., & Clark, M. A. (2002) · PubMed · Cited by 57 · see citing works
Self-citationChen, T., Nines, R. G., Peschke, S. M., Kresty, L. A., & Stoner, G. D. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-0302 · Cited by 56 · see citing works
The Effect of Arginase on the Retardation of Tumour Growth
Bach, S. J., & Swaine, D. (1965) · British Journal of Cancer · doi:10.1038/bjc.1965.45 · Cited by 55 · see citing works
Gong, H., Pöttgen, C., Stüben, G., Havers, W., Stuschke, M., & Schweigerer, L. (2003) · International Journal of Cancer · doi:10.1002/ijc.11298 · Cited by 53 · see citing works
The best way to use asparaginase in childhood acute lymphatic leukaemia – still to be defined?
Pinheiro, J. P. V., & Boos, J. (2004) · British Journal of Haematology · doi:10.1111/j.1365-2141.2004.04863.x · Cited by 52 · see citing works
Noh, E. J., Kang, S. W., Shin, Y. J., Kim, D. C., Park, I. S., Kim, M. Y., Chun, B. G., & Min, B.-H. (2002) · Molecules and Cells · doi:10.1016/s1016-8478(23)15015-1 · Cited by 49 · see citing works
Agarwala, S. S., & Kirkwood, J. M. (1998) · Seminars in Surgical Oncology · doi:10.1002/(sici)1098-2388(199806)14:4 · Cited by 46 · see citing works
Holley, R. W. (1967) · Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis · doi:10.1016/0005-2787(67)90076-7 · Cited by 43 · see citing works
Noh, E., Kang, S., Shin, Y., Choi, S., Kim, C., Park, I.-S., Wheatley, D. N., & Min, B. (2004) · International Journal of Cancer · doi:10.1002/ijc.20435 · Cited by 40 · see citing works
THOMAS, J. B., Holtsberg, F. W., Ensor, M., Bomalaski, J. S., & Clark, M. A. (2002) · Biochemical Journal · doi:10.1042/0264-6021:3630581 · Cited by 39 · see citing works
Self-citationTakaku, H., Misawa, S., Hayashi, H., & Miyazaki, K. (1993) · Japanese Journal of Cancer Research · doi:10.1111/j.1349-7006.1993.tb02821.x · Cited by 38 · see citing works
Apoptotic cell death of human T lymphoblastoid cells induced by arginine deiminase.
Komada (1997) · International Journal of Hematology · doi:10.1016/s0925-5710(96)00538-5 · Cited by 36 · see citing works
The influence of arginine upon the growth rate of a transplantable tumour in the mouse
Gilroy, E. (1930) · Biochemical Journal · doi:10.1042/bj0240589 · Cited by 35 · see citing works
Regression of hepatocellular cancer in a patient treated with arginine deiminase.
Curley, S. A., Bomalaski, J. S., Ensor, M., Holtsberg, F. W., & Clark, M. A. (2003) · PubMed · Cited by 34 · see citing works
Self-citationTHOMAS, J. B., Holtsberg, F. W., Ensor, M., et al. (2002) · Biochemical Journal · doi:10.1042/bj3630581 · Cited by 34 · see citing works
Self-citationShen, L., Lin, W., Beloussow, K., Hosoya, K., Terasaki, T., Ann, D. K., & Shen, W. (2003) · Biochemical Pharmacology · doi:10.1016/s0006-2952(03)00555-0 · Cited by 32 · see citing works
Pemetrexed: Single-agent and combination phase I study overview
Boyer, M. J., Rivory, L. P., & Clarke, S. J. (2002) · Seminars in Oncology · doi:10.1053/sonc.2002.37464 · Cited by 16 · see citing works
Update on the systemic treatment of malignant melanoma
Lawson, D. H. (2004) · Seminars in Oncology · doi:10.1053/j.seminoncol.2004.02.014 · Cited by 14 · see citing works
The systemic treatment of advanced cutaneous melanoma
Logan, T. F. (2003) · Facial Plastic Surgery Clinics of North America · doi:10.1016/s1064-7406(02)00056-1 · Cited by 10 · see citing works
Self-citationFeun, L. G., Savaraj, N., Hurley, J. E., & Marini, A. (2002) · Cancer Investigation · doi:10.1081/cnv-120001181 · Cited by 7 · see citing works
Self-citationThe role of biological response modifiers in malignant melanoma
Lens, M. B. (2003) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.3.8.1225 · Cited by 6 · see citing works
Adjuvant therapy of melanoma: what's new?
Ascierto, P. A., Palmieri, G., Daponte, A., Melucci, M. T., Satriano, R. A., Mozzillo, N., & Castello, G. (2002) · Melanoma Research · doi:10.1097/00008390-200206000-00015 · Cited by 4 · see citing works
Self-citationInhibitory effects of arginase on mammary adenocarcinoma transplants in strain "A" mice.
VRAT, V. (1951) · Permanente Foundation Medical Bulletin · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Factors affecting the clearance and biodistribution of polymeric nanoparticles
Alexis, F., Pridgen, E., Molnar, L. K., & Farokhzad, O. C. (2008) · Molecular Pharmaceutics · doi:10.1021/mp800051m · Cited by 3,699 · see citing works
Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy
Pérez‐Herrero, E., & Fernández‐Medarde, A. (2015) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2015.03.018 · Cited by 1,888 · see citing works
Cancer metabolism: a therapeutic perspective
Martinez-Outschoorn, U. E., Peiris-Pagés, M., Pestell, R. G., Sotgia, F., & Lisanti, M. P. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.60 · Cited by 1,505 · see citing works
Targeting Metabolism for Cancer Therapy
Luengo, A., Gui, D. Y., & Vander Heiden, M. G. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.08.028 · Cited by 971 · see citing works
Arginase: an emerging key player in the mammalian immune system
Munder, M. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00291.x · Cited by 701 · see citing works
Delivery of Therapeutic Proteins
Pisal, D. S., Kosloski, M. P., & Balu-Iyer, S. V. (2010) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22054 · Cited by 532 · see citing works
PEG conjugates in clinical development or use as anticancer agents: An overview
Pasut, G., & Veronese, F. M. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.02.010 · Cited by 458 · see citing works
Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer
Delage, B., Fennell, D. A., Nicholson, L., McNeish, I., Lemoine, N. R., Crook, T., & Szlosarek, P. W. (2010) · International Journal of Cancer · doi:10.1002/ijc.25202 · Cited by 441 · see citing works
Immune resistance orchestrated by the tumor microenvironment
Gajewski, T. F., Meng, Y., Blank, C., Brown, I., Kacha, A., Kline, J., & Harlin, H. (2006) · Immunological Reviews · doi:10.1111/j.1600-065x.2006.00442.x · Cited by 437 · see citing works
Myeloid Cell-Derived Arginase in Cancer Immune Response
Grzywa, T. M., Sosnowska, A., Matryba, P., Rydzyńska, Z., Jasiński, M., Nowis, D., & Gołąb, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00938 · Cited by 434 · see citing works
PEGylation in anti-cancer therapy: An overview
Mishra, P., Nayak, B., & Dey, R. K. (2015) · Asian Journal of Pharmaceutical Sciences · doi:10.1016/j.ajps.2015.08.011 · Cited by 383 · see citing works
Nanoparticle Technologies for Cancer Therapy
Alexis, F., Pridgen, E. M., Langer, R., & Farokhzad, O. C. (2009) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-00477-3_2 · Cited by 372 · see citing works
Rewiring urea cycle metabolism in cancer to support anabolism
Keshet, R., Szlosarek, P. W., Carracedo, A., & Erez, A. (2018) · Nature reviews. Cancer · doi:10.1038/s41568-018-0054-z · Cited by 322 · see citing works
Kim, R. H., Coates, J. M., Bowles, T. L., McNerney, G. P., Sutcliffe-Goulden, J., Jung, J. U., Gandour‐Edwards, R. F., Chuang, F. Y. S., Bold, R. J., & Kung, H.-J. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-3157 · Cited by 316 · see citing works
Arginine Metabolism in Myeloid Cells Shapes Innate and Adaptive Immunity
Rodrı́guez, P. C., Ochoa, A. C., & Al-Khami, A. A. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00093 · Cited by 287 · see citing works
Cheng, P., Lam, T. L., Lam, W.-M., Tsui, S. M., Cheng, A. W. M., Lo, W. H., & Leung, Y. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-1945 · Cited by 279 · see citing works
Arginine dependence of tumor cells: targeting a chink in cancer’s armor
Patil, M. D., Bhaumik, J., Babykutty, S., Banerjee, U. C., & Fukumura, D. (2016) · Oncogene · doi:10.1038/onc.2016.37 · Cited by 268 · see citing works
Immune Suppression in the Tumor Microenvironment
Gajewski, T. F., Meng, Y., & Harlin, H. (2006) · Journal of Immunotherapy · doi:10.1097/01.cji.0000199193.29048.56 · Cited by 261 · see citing works
Amino acid metabolism in hematologic malignancies and the era of targeted therapy
Tabe, Y., Lorenzi, P. L., & Konopleva, M. Y. (2019) · Blood · doi:10.1182/blood.2019001034 · Cited by 238 · see citing works
Arginine Deprivation as a Targeted Therapy for Cancer
Feun, L. G., You, M., Wu, C., Kuo, M. T., Wangpaichitr, M., Spector, S. A., & Savaraj, N. (2008) · Current Pharmaceutical Design · doi:10.2174/138161208784246199 · Cited by 235 · see citing works
Self-citationTsai, W.-B., Aiba, I., Long, Y., Lin, H., Feun, L. G., Savaraj, N., & Kuo, M. T. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-3605 · Cited by 233 · see citing works
Self-citationTargeting arginine-dependent cancers with arginine-degrading enzymes: opportunities and challenges
Phillips, M. M., Sheaff, M. T., & Szlosarek, P. W. (2013) · Cancer Research and Treatment · doi:10.4143/crt.2013.45.4.251 · Cited by 229 · see citing works
Arginine Starvation Impairs Mitochondrial Respiratory Function in ASS1-Deficient Breast Cancer Cells
Qiu, F., Chen, Y.-R., Liu, X., Chu, C.-Y., Shen, L., Xu, J., Gaur, S., Forman, H. J., Zhang, H., Zheng, S. S., et al. (2014) · Science Signaling · doi:10.1126/scisignal.2004761 · Cited by 218 · see citing works
The Diverse Functions of Non-Essential Amino Acids in Cancer
Choi, B.-H., & Coloff, J. L. (2019) · Cancers · doi:10.3390/cancers11050675 · Cited by 213 · see citing works
Szlosarek, P. W., Steele, J. P. C., Nolan, L., Gilligan, D., Taylor, P. D., Spicer, J. F., Lind, M., Mitra, S. S., Shamash, J., Phillips, M. M., et al. (2016) · JAMA Oncology · doi:10.1001/jamaoncol.2016.3049 · Cited by 203 · see citing works
Self-citationIL‐8 induces exocytosis of arginase 1 by neutrophil polymorphonuclears in nonsmall cell lung cancer
Rotondo, R., Barisione, G., Mastracci, L., Grossi, F., Orengo, A. M., Costa, R., Truini, M., Fabbi, M., Ferrini, S., & Barbieri, O. (2009) · International Journal of Cancer · doi:10.1002/ijc.24448 · Cited by 198 · see citing works
Targeting amino acid metabolism in cancer growth and anti-tumor immune response
Ananieva, E. A. (2015) · World Journal of Biological Chemistry · doi:10.4331/wjbc.v6.i4.281 · Cited by 198 · see citing works
Changou, C. A., Chen, Y.-R., Xing, L., Yen, Y., Chuang, F. Y. S., Cheng, R. H., Bold, R. J., Ann, D. K., & Kung, H.-J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1404171111 · Cited by 186 · see citing works
Glazer, E. S., Piccirillo, M., Albino, V., Giacomo, R. D., Palaia, R., Mastro, A. A., Beneduce, G., Castello, G., Rosa, V. D., Petrillo, A., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.7765 · Cited by 187 · see citing works
Self-citationSzlosarek, P. W., Klampatsa, A., Pallaska, A., Sheaff, M. T., Smith, P., Crook, T., Grimshaw, M. J., Steele, J. P. C., Rudd, R., Balkwill, F. R., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1101 · Cited by 181 · see citing works
Argininosuccinate synthase: at the center of arginine metabolism.
(2011) · Europe PMC (PubMed Central) · Cited by 176 · see citing works
Arginine—Dual roles as an onconutrient and immunonutrient
Albaugh, V. L., Pinzon‐Guzman, C., & Barbul, A. (2016) · Journal of Surgical Oncology · doi:10.1002/jso.24490 · Cited by 173 · see citing works
Drug-induced amino acid deprivation as strategy for cancer therapy
Fung, M. K. L., & Chan, G. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0509-9 · Cited by 172 · see citing works
Yoon, C., Shim, Y., Kim, E., Lee, J., Won, N., Kim, J., Park, I., Yoon, D., & Min, B. (2007) · International Journal of Cancer · doi:10.1002/ijc.22322 · Cited by 165 · see citing works
Arginine and the metabolic regulation of nitric oxide synthesis in cancer
Keshet, R., & Erez, A. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.033332 · Cited by 159 · see citing works
Arginine metabolism and deprivation in cancer therapy
Zou, S., Wang, X., Liu, P., Ke, C., & Xu, S. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109210 · Cited by 159 · see citing works
Targeting arginine metabolism pathway to treat arginine-dependent cancers
Qiu, F., Huang, J., & Sui, M. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.04.020 · Cited by 158 · see citing works
Metabolic pathways of L-arginine and therapeutic consequences in tumors
Szefel, J., Danielak, A., & Kruszewski, W. J. (2018) · Advances in Medical Sciences · doi:10.1016/j.advms.2018.08.018 · Cited by 155 · see citing works
Bowles, T. L., Kim, R., Galante, J., Parsons, C. M., Virudachalam, S., Kung, H., & Bold, R. J. (2008) · International Journal of Cancer · doi:10.1002/ijc.23723 · Cited by 153 · see citing works
Allen, M. D., Luong, P., Hudson, C. D., Leyton, J., Delage, B., Ghazaly, E. A., Cutts, R. J., Yuan, M., Syed, N., Nigro, C. L., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-1702 · Cited by 153 · see citing works
Self-citationAnti-cancer PEG-enzymes: 30 years old, but still a current approach
Pasut, G., Sergi, M., & Veronese, F. M. (2007) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.04.018 · Cited by 152 · see citing works
Phase I/II study of pegylated arginine deiminase (ADI-PEG 20) in patients with advanced melanoma
Ott, P. A., Carvajal, R. D., Pandit-Taskar, N., Jungbluth, A. A., Hoffman, E. W., Wu, B.-W., Bomalaski, J. S., Venhaus, R., Pan, L., Old, L. J., et al. (2013) · Investigational New Drugs · doi:10.1007/s10637-012-9862-2 · Cited by 146 · see citing works
Self-citationDelage, B., Luong, P., Maharaj, L., Ó’Riain, C., Syed, N., Crook, T., Hatzimichael, E. C., Papoudou‐Bai, A., Mitchell, T. J., Whittaker, S. J., et al. (2012) · Cell Death and Disease · doi:10.1038/cddis.2012.83 · Cited by 144 · see citing works
Self-citationTsai, W.-B., Aiba, I., Lee, S.-Y., Feun, L. G., Savaraj, N., & Kuo, M. T. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0794 · Cited by 141 · see citing works
Self-citationMiraki‐Moud, F., Ghazaly, E. A., Ariza‐McNaughton, L., Hodby, K. A., Clear, A. J., Anjos‐Afonso, F., Liapis, K., Grantham, M., Sohrabi, F., Cavenagh, J. D., et al. (2015) · Blood · doi:10.1182/blood-2014-10-608133 · Cited by 139 · see citing works
Self-citationNicholson, L. J., Smith, P. R., Hiller, L., Szlosarek, P. W., Kimberley, C., Sehouli, J., Koensgen, D., Mustea, A., Schmid, P., & Crook, T. (2009) · International Journal of Cancer · doi:10.1002/ijc.24546 · Cited by 133 · see citing works
Buijs, N., de van der Schueren, M. A. E., Langius, J. A. E., Leemans, C. R., Kuik, D. J., Vermeulen, M. A. R., & van Leeuwen, P. A. M. (2010) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2010.29532 · Cited by 124 · see citing works
Beddowes, E. J., Spicer, J. F., Chan, P. Y., Khadeir, R. S., Corbacho, J. G., Repana, D., Steele, J. P. C., Schmid, P., Szyszko, T. A., Cook, G., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.71.3230 · Cited by 121 · see citing works
Self-citationKobayashi, E., Masuda, M., Nakayama, R. T., Ichikawa, H., Satow, R., Shitashige, M., Honda, K., Yamaguchi, U., Shoji, A., Tochigi, N., et al. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0774 · Cited by 120 · see citing works
Pegylated arginine deiminase: a novel anticancer enzyme agent
Feun, L. G., & Savaraj, N. (2006) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.15.7.815 · Cited by 118 · see citing works
Self-citationKelly, M. P., Jungbluth, A. A., Wu, B.-W., Bomalaski, J. S., Old, L. J., & Ritter, G. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.524 · Cited by 117 · see citing works
Self-citationFeun, L. G., Marini, A., Walker, G., Elgart, G., Moffat, F., Rodgers, S. E., Wu, C. J., You, M., Wangpaichitr, M., Kuo, M. T., et al. (2012) · British Journal of Cancer · doi:10.1038/bjc.2012.106 · Cited by 113 · see citing works
Self-citationArginine Deprivation, Autophagy, Apoptosis (AAA) for the Treatment of Melanoma
Savaraj, N., You, M., Wu, C., Wangpaichitr, M., Kuo, M. T., & Feun, L. G. (2010) · Current Molecular Medicine · doi:10.2174/156652410791316995 · Cited by 108 · see citing works
Self-citationPegylated arginase I: a potential therapeutic approach in T-ALL
Hernandez, C. P., Morrow, K. D., Lopez-Barcons, L. A., Zabaleta, J., Sierra, R. A., Velasco, C., COLE, J. T., & Rodrı́guez, P. C. (2010) · Blood · doi:10.1182/blood-2009-12-258822 · Cited by 104 · see citing works
Yau, T. C. C., Cheng, P. N.-M., Chan, P., Chan, W., Chen, L., Yuen, J. H. F., Pang, R. W. C., Fan, S. T., & Poon, R. T. P. (2012) · Investigational New Drugs · doi:10.1007/s10637-012-9807-9 · Cited by 104 · see citing works
Wangpaichitr, M., Sullivan, E. J., Theodoropoulos, G., Wu, C., You, M., Feun, L. G., Lampidis, T. J., Kuo, M. T., & Savaraj, N. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0599 · Cited by 94 · see citing works
Self-citationInhibition of arginase modulates T-cell response in the tumor microenvironment of lung carcinoma
Sosnowska, A., Chlebowska, J., Matryba, P., Pilch, Z., Greig, A., Wolny, A., Grzywa, T. M., Rydzyńska, Z., Sokołowska, O., Rygiel, T. P., et al. (2021) · OncoImmunology · doi:10.1080/2162402x.2021.1956143 · Cited by 92 · see citing works
Tomlinson, B. K., Thomson, J. A., Bomalaski, J. S., Diaz, M., Akande, T., Mahaffey, N., Li, T., Dutia, M. P., Kelly, K. L., Gong, I.-Y., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2610 · Cited by 91 · see citing works
Self-citationAmino acid deprivation using enzymes as a targeted therapy for cancer and viral infections
Fernandes, H. S., Teixeira, C. S. S., Fernandes, P. A., Ramos, M. J., & Cerqueira, N. M. F. S. A. (2016) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2017.1254194 · Cited by 91 · see citing works
Microbial-based therapy of cancer: Current progress and future prospects
Bernardes, N., Seruca, R., Chakrabarty, A. M., & Fialho, A. M. (2010) · Bioengineered Bugs · doi:10.4161/bbug.1.3.10903 · Cited by 88 · see citing works
Riess, C., Shokraie, F., Classen, C. F., Kreikemeyer, B., Fiedler, T., Junghanß, C., & Maletzki, C. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000495382 · Cited by 86 · see citing works
Lam, T. L., Wong, G., Chong, H.-C., Cheng, P. N.-M., Choi, S. C., Chow, T. L., Kwok, S.-Y., Poon, R. T. P., Wheatley, D. N., Lo, W., et al. (2009) · Cancer Letters · doi:10.1016/j.canlet.2008.11.031 · Cited by 87 · see citing works
Deprivation of arginine by recombinant human arginase in prostate cancer cells
Hsueh, E. C., Knebel, S. M., Lo, W., Leung, Y., Cheng, P. N.-M., & Hsueh, C.-T. (2012) · Journal of Hematology & Oncology · doi:10.1186/1756-8722-5-17 · Cited by 84 · see citing works
Dual-Porosity Hollow Nanoparticles for the Immunoprotection and Delivery of Nonhuman Enzymes
Ortac, I., Simberg, D., Yeh, Y.-S., Yang, J., Messmer, B. T., Trogler, W. C., Tsien, R. Y., & Esener, S. C. (2014) · Nano Letters · doi:10.1021/nl404360k · Cited by 79 · see citing works
Mimi, H., Ho, K. M., Siu, Y. S., Wu, A., & Li, P. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2011.10.035 · Cited by 79 · see citing works
Amino acid metabolism as a therapeutic target in cancer: a review
Endicott, M., Jones, M. J., & Hull, J. (2021) · Amino Acids · doi:10.1007/s00726-021-03052-1 · Cited by 75 · see citing works
Progress in the Management of Malignant Pleural Mesothelioma in 2017
McCambridge, A. J., Napolitano, A., Mansfield, A. S., Fennell, D. A., Sekido, Y., Nowak, A. K., Reungwetwattana, T., Mao, W., Pass, H. I., Carbone, M., et al. (2018) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2018.02.021 · Cited by 75 · see citing works
Tsui, S. M., Lam, W.-M., Lam, T. L., Chong, H.-C., So, P., Kwok, S.-Y., Arnold, S., Cheng, P. N.-M., Wheatley, D. N., Lo, W., et al. (2009) · Cancer Cell International · doi:10.1186/1475-2867-9-9 · Cited by 75 · see citing works
Szlosarek, P. W., Luong, P., Phillips, M. M., Baccarini, M., Ellis, S. M., Szyszko, T. A., Sheaff, M. T., & Avril, N. E. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.42.1784 · Cited by 74 · see citing works
You, M., Savaraj, N., Kuo, M. T., Wangpaichitr, M., Varona-Santos, J., Wu, C., Nguyen, D. M., & Feun, L. G. (2012) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-012-1518-1 · Cited by 72 · see citing works
Self-citationHall, P. E., Lewis, R., Syed, N., Shaffer, R. E., Evanson, J., Ellis, S. M., Williams, M., Feng, X., Johnston, A. L., Thomson, J. A., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-3729 · Cited by 70 · see citing works
Self-citationNitric Oxide and Its Gatekeeper Thrombospondin-1 in Tumor Angiogenesis
Roberts, D. D., Isenberg, J. S., Ridnour, L. A., & Wink, D. A. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1758 · Cited by 68 · see citing works
McAlpine, J. A., Lu, H.-T., Wu, K. C., Knowles, S. K., & Thomson, J. A. (2014) · BMC Cancer · doi:10.1186/1471-2407-14-621 · Cited by 67 · see citing works
Wang, Z., Shi, X., Li, Y., Fan, J., Zeng, X. L., Xian, Z., Wang, Z., Sun, Y., Wang, S., Song, P., et al. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.503 · Cited by 67 · see citing works
Cancer cell metabolism: Rewiring the mitochondrial hub
Oliveira, G. L., Coelho, A. R., Marques, R., & Oliveira, P. J. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.166016 · Cited by 62 · see citing works
Khoury, O., Ghazale, N., Stone, E. M., El‐Sibai, M., Frankel, A. E., & Abi‐Habib, R. J. (2015) · Journal of Neuro-Oncology · doi:10.1007/s11060-014-1698-5 · Cited by 64 · see citing works
Insights into the Pathogenesis and Treatment of Cancer from Inborn Errors of Metabolism
Erez, A., Shchelochkov, O. A., Plon, S. E., Scaglia, F., & Lee, B. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.03.005 · Cited by 65 · see citing works
Pegargiminase Plus First-Line Chemotherapy in Patients With Nonepithelioid Pleural Mesothelioma
Szlosarek, P. W., Creelan, B., Sarkodie, T., Nolan, L., Taylor, P. D., Olevsky, O. M., Grosso, F., Cortinovis, D. L., Chitnis, M. M., Roy, A., et al. (2024) · JAMA Oncology · doi:10.1001/jamaoncol.2023.6789 · Cited by 61 · see citing works
Self-citationAberrant regulation of argininosuccinate synthetase by TNF‐α in human epithelial ovarian cancer
Szlosarek, P. W., Grimshaw, M. J., Wilbanks, G. D., Hagemann, T., Wilson, J. L., Burke, F., Stamp, G., & Balkwill, F. R. (2007) · International Journal of Cancer · doi:10.1002/ijc.22666 · Cited by 61 · see citing works
Habibi, D., Ogloff, N., Jalili, R. B., Yost, A., Weng, A. P., Ghahary, A., & Ong, C. J. (2011) · Investigational New Drugs · doi:10.1007/s10637-011-9700-y · Cited by 60 · see citing works
Romero, P. A., Stone, E. M., Lamb, C., Chantranupong, L., Krause, A., Miklos, A. E., Hughes, R. A., Fechtel, B. M., Ellington, A. D., Arnold, F. H., et al. (2012) · ACS Synthetic Biology · doi:10.1021/sb300014t · Cited by 60 · see citing works
Argininosuccinate synthase 1 is an intrinsic Akt repressor transactivated by p53
Miyamoto, T., Lo, P. H. Y., Saichi, N., Ueda, K., Hirata, M., Tanikawa, C., & Matsuda, K. (2017) · Science Advances · doi:10.1126/sciadv.1603204 · Cited by 59 · see citing works
Shan, Y., Hsu, H., Lai, M.-D., Yen, M., Chen, W.-C., Fang, J.-H., Weng, T., & Chen, Y. (2015) · Scientific Reports · doi:10.1038/srep09783 · Cited by 58 · see citing works
Arginine metabolism: a potential target in pancreatic cancer therapy
Yang, J., Wang, C., Qiu, J., Ren, B., & You, L. (2020) · Chinese Medical Journal · doi:10.1097/cm9.0000000000001216 · Cited by 56 · see citing works
Tanios, R. F., Bekdash, A., Kassab, E., Stone, E. M., Georgiou, G., Frankel, A. E., & Abi‐Habib, R. J. (2013) · Leukemia Research · doi:10.1016/j.leukres.2013.08.007 · Cited by 55 · see citing works
Engineering Reduced-Immunogenicity Enzymes for Amino Acid Depletion Therapy in Cancer
Cantor, J. R., Panayiotou, V., Agnello, G., Georgiou, G., & Stone, E. M. (2011) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-416039-2.00015-x · Cited by 53 · see citing works
Zhang, Y., Chung, S., Tam, S.-Y., Leung, Y., & Guan, X. (2021) · Cancer Letters · doi:10.1016/j.canlet.2020.12.041 · Cited by 52 · see citing works
Arginine deprivation therapy for malignant melanoma
Kim, K., Yoon, Y., Frankel, A. E., Feun, & Ekmekcioglu (2012) · Clinical Pharmacology Advances and Applications · doi:10.2147/cpaa.s37350 · Cited by 50 · see citing works
Anti-leukemic mechanisms of pegylated arginase I in acute lymphoblastic T-cell leukemia
Morrow, K. D., Hernandez, C. P., Raber, P. L., Valle, L. D., Wilk, A. M., Majumdar, S., Wyczechowska, D. D., Krzysztof Reiss, F., & Rodrı́guez, P. C. (2012) · Leukemia · doi:10.1038/leu.2012.247 · Cited by 50 · see citing works
long, Y. N., Tsai, W.-B., Wang, D., Hawke, D. H., Savaraj, N., Feun, L. G., Hung, M., Chen, H. H. W., & Kuo, M. T. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.11.028 · Cited by 51 · see citing works
Self-citationAmino Acid Degrading Enzymes and their Application in Cancer Therapy
Pokrovsky, V. S., Chepikova, O. E., Давыдов, Д. Ж., Zamyatnin, A. A., Lukashev, A. N., & Lukasheva, E. V. (2017) · Current Medicinal Chemistry · doi:10.2174/0929867324666171006132729 · Cited by 50 · see citing works
Vynnytska‐Myronovska, B., Bobak, Y. P., Garbe, Y., Dittfeld, C., Stasyk, O. V., & Kunz‐Schughart, L. A. (2011) · International Journal of Cancer · doi:10.1002/ijc.26221 · Cited by 48 · see citing works
Chang, K., Chiang, N., Wu, S., Yen, C.-J., Chen, S., Yeh, Y., Li, C., Feng, X., Wu, K., Johnston, A. L., et al. (2021) · OncoImmunology · doi:10.1080/2162402x.2021.1943253 · Cited by 47 · see citing works
Self-citationKim, J., Jeong, D., & Lee, H. J. (2006) · Protein Expression and Purification · doi:10.1016/j.pep.2006.12.002 · Cited by 47 · see citing works
Synakiewicz, A., Stachowicz‐Stencel, T., & Adamkiewicz‐Drożyńska, E. (2014) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2014.934808 · Cited by 45 · see citing works
Research into cancer metabolomics: Towards a clinical metamorphosis
Olivares, O., Däbritz, J. H. M., King, A., Gottlieb, E., & Halsey, C. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.09.008 · Cited by 45 · see citing works
Rotondo, R., Mastracci, L., Piazza, T., Barisione, G., Fabbi, M., Cassanello, M., Costa, R., Morandi, B., Astigiano, S., Cesario, A., et al. (2008) · International Journal of Cancer · doi:10.1002/ijc.23437 · Cited by 45 · see citing works
Expression of argininosuccinate synthetase in patients with hepatocellular carcinoma
Wu, L., Li, L., Meng, S.-C., Qi, R., Mao, Z., & Lin, M. T. (2012) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.12043 · Cited by 44 · see citing works
Arginine deprivation induces endoplasmic reticulum stress in human solid cancer cells
Bobak, Y. P., Kurlishchuk, Y. V., Vynnytska‐Myronovska, B., Grydzuk, O., Shuvayeva, G., Rędowicz, M. J., Kunz‐Schughart, L. A., & Stasyk, O. V. (2015) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2015.10.027 · Cited by 44 · see citing works
D, S. M. M., & Nitti, D. (2007) · Medicinal Research Reviews · doi:10.1002/med.20110 · Cited by 44 · see citing works
- Authors
- Ascierto, P. A., Scala, S., Castello, G., Daponte, A., Simeone, E., Ottaiano, A., Beneduce, G., De Rosa, V., Izzo, F., Melucci, M. T., Ensor, C. M., Prestayko, A. W., Holtsberg, F. W., Bomalaski, J. S., Clark, M. A., Savaraj, N., Feun, L. G., & Logan, T. F.
- Affiliations
- University of Kentucky (US)
- From the Pascale National Cancer Institute, Naples, Italy; Phoenix Pharmacologics, Inc; University of Kentucky, Lexington, KY; Hematology and Oncology Division, University of Miami; Miami Veterans Affairs Medical Center, Miami, FL; and Hematology and Oncology Division, Indiana University, Indianapolis, IN.
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2005-10-20
- Volume
- 23
- Issue
- 30
- Pages
- 7660-7668
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2167874373
- Cited by
- 238
- References
- 53
- Citations by year
- 2025: 8 · 2024: 7 · 2023: 10 · 2022: 10 · 2021: 13 · 2020: 17 · 2019: 8 · 2018: 10 · 2017: 13 · 2016: 15 · 2015: 16 · 2014: 15 · 2013: 14 · 2012: 19
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Keywords
- metastatic melanoma, arginine deiminase, pegylated arginine deiminase, arginine auxotrophy, nitric oxide, enzyme conjugation, pharmacokinetics, pharmacodynamics, anticancer activity, dose escalation, safety and tolerability
- MeSH terms
- Adult, Aged, Aged, 80 and over, Arginine, Female, Humans, Hydrolases, Italy, Male, Melanoma, Middle Aged, Nitric Oxide, Polyethylene Glycols, Skin Neoplasms, United States, Survival Rate, Treatment Outcome, Maximum Tolerated Dose
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review