Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase

Hepatogastroenterology

Sumiyoshi, K., Sato, N., Akagawa, S., Hirano, T., Koikawa, K., Horioka, K., Ozono, K., Fujiwara, K., Tanaka, M., & Sada, M. (2011) · Hepatogastroenterology · doi:10.5754/hge11125 · Cited by 2,450 · 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

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

Arginine Deiminase as a Novel Therapy for Prostate Cancer Induces Autophagy and Caspase-Independent Apoptosis

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

Pegylated arginine deiminase (ADI-SS PEG20,000 mw) inhibits human melanomas and hepatocellular carcinomas in vitro and in vivo.

Ensor, M., Holtsberg, F. W., Bomalaski, J. S., & Clark, M. A. (2002) · PubMed · Cited by 315 · see citing works

Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: results from phase I/II studies

Izzo, 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

I. Arginine

Tapiero, 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

Pegylated arginine deiminase treatment of patients with metastatic melanoma: results from phase I and II studies

Ascierto, P. A., Scala, S., Castello, G., Daponte, A., Simeone, E., Ottaiano, A., Beneduce, G., De Rosa, V., Izzo, F., Melucci, M. T., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.02.0933 · 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

In vivo Loss of Expression of Argininosuccinate Synthetase in Malignant Pleural Mesothelioma Is a Biomarker for Susceptibility to Arginine Depletion

Szlosarek, 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

Renal cell carcinoma does not express argininosuccinate synthetase and is highly sensitive to arginine deprivation<i>via</i>arginine deiminase

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

Poly(ethylene glycol) (PEG) conjugated arginine deiminase: effects of PEG formulations on its pharmacological properties

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

Pancreatic cancer cell lines deficient in argininosuccinate synthetase are sensitive to arginine deprivation by arginine deiminase

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

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

Resistance to arginine deiminase treatment in melanoma cells is associated with induced argininosuccinate synthetase expression involving c-Myc/HIF-1α/Sp4

Tsai, 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

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

Arginine 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

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

Controlling cancer by restricting arginine availability–arginine-catabolizing enzymes as anticancer agents

Wheatley, D. N. (2004) · Anti-Cancer Drugs · doi:10.1097/00001813-200410000-00002 · Cited by 74 · see citing works

Resistance to the anti-proliferative activity of recombinant arginine deiminase in cell culture correlates with the endogenous enzyme, argininosuccinate synthetase

Shen, L.-J., Lin, W.-C., Beloussow, K., & Shen, W.-C. (2003) · Cancer Letters · doi:10.1016/s030-43835(02)00693-6 · Cited by 66 · 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

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

The relationship of arginine deprivation, argininosuccinate synthetase and cell death in melanoma.

Savaraj, N., Wu, C., Kuo, M. T., You, M., Wangpaichitr, M., Robles, C., Spector, S. A., & Feun, L. G. (2007) · Europe PMC (PubMed Central) · Cited by 32 · see citing works

The Relationship of Arginine Deprivation, Argininosuccinate Synthetase and Cell Death in Melanoma

Savaraj, N., Wu, C., Kuo, M. T., You, M., Wangpaichitr, M., Robles, C., Spector, S. A., & Feun, L. G. (2007) · Drug Target Insights · doi:10.1177/117739280700200016 · Cited by 30 · see citing works

The combination of ADI-PEG20 and TRAIL effectively increases cell death in melanoma cell lines

You, M., Savaraj, N., Wangpaichitr, M., Wu, C., Kuo, M. T., Varona-Santos, J., Nguyen, D. M., & Feun, L. G. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.03.066 · Cited by 29 · see citing works

Anti-tumor activity of arginine deiminase via arginine deprivation in retinoblastoma

Kim, J. H., Kim, J. H., Yu, Y. S., Kim, D. W., Min, B.-H., & Kim, K.-W. (2007) · Oncology Reports · doi:10.3892/or.18.6.1373 · Cited by 26 · see citing works

Radiation Recall 5 Years After Whole-Breast Irradiation for Early-Stage Breast Cancer Secondary to Initiation of Rosuvastatin and Amlodipine

Taunk, N. K., Haffty, B. G., & Goyal, S. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.35.7202 · Cited by 16 · see citing works

G-quartet oligonucleotides: A new class of Stat3 inhibitors that suppresses growth of prostate and breast tumors through induction of apoptosis

Feun, L. G., Wu, C., Clark, M. E., Bombalaski, J., Holtsberg, F. W., Wangpaijit, M., Robles, C., & Savaraj, N. (2004) · Cancer Research · Cited by 16 · see citing works

Phase I/II study of arginine deiminase (ADI-PEG 20) in patients with advanced malignant melanoma (MM)

Ott, P. A., Carvajal, R. D., Pandit-Taskar, N. D., Jungbluth, A. A., Hoffman, E. W., Venhaus, R. R., Pan, L., Old, L. J., Pavlick, A. C., & Wolchok, J. D. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.15_suppl.9030 · Cited by 5 · see citing works

Determining argininosuccinate synthetase (ASS) expression in patients with melanoma treated with arginine depleting therapy.

Dinh, V., You, M., Savaraj, N., Wu, C., Kuo, M. T., Wangpaichitr, M., & Feun, L. G. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.29.15_suppl.10627 · Cited by 4 · see citing works

Clinical and pharmacologic study of ADI-PEG20 in hepatocellular carcinoma

Feun, L. G., Savaraj, N., Wu, C., You, M., Wangpaichitr, M., Marini, A., Levi, D., Bomalaski, J. S., & Kuo, M. T. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.26.15_suppl.15584 · Cited by 2 · see citing works

Abstract 4096: TRAIL enhances cytotoxicity of arginine depletion therapy in argininosuccinate synthetase-negative melanoma cells through interruption of autophagy via activation of caspases

You, M., Savaraj, N., Wangpaichitr, M., Wu, C., Kuo, M. T., & Feun, L. G. (2011) · Cancer Research · doi:10.1158/1538-7445.am2011-4096 · Cited by 1 · 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

Metabolism of Amino Acids in Cancer

Wei, Z. C., Liu, X., Cheng, C., Yu, W., & Yi, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.603837 · Cited by 439 · see citing works

Autophagy maintains tumour growth through circulating arginine

Poillet-Perez, L., Xie, X., Zhan, L., Yang, Y., Sharp, D. W., Hu, Z. S., Su, X., Maganti, A., Jiang, C., Lu, W., et al. (2018) · Nature · doi:10.1038/s41586-018-0697-7 · Cited by 363 · see citing works

Arginine Signaling and Cancer Metabolism

Chen, C., Hsu, S.-C., Ann, D. K., Yen, Y., & Kung, H.-J. (2021) · Cancers · doi:10.3390/cancers13143541 · Cited by 276 · 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

Phase III randomized study of second line ADI-PEG 20 plus best supportive care versus placebo plus best supportive care in patients with advanced hepatocellular carcinoma

Abou‐Alfa, G. K., Qin, S., Ryoo, B., Lu, S., Yen, C.-J., Feng, Y., Lim, H. Y., Izzo, F., Colombo, M., Sarker, D., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy101 · Cited by 236 · see citing works

Targeting 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 Deprivation With Pegylated Arginine Deiminase in Patients With Argininosuccinate Synthetase 1–Deficient Malignant Pleural Mesothelioma

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

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

Arginine Deprivation Inhibits the Warburg Effect and Upregulates Glutamine Anaplerosis and Serine Biosynthesis in ASS1-Deficient Cancers

Kremer, J. C., Prudner, B. C., Lange, S. E. S., Bean, G. R., Schultze, M., Brashears, C. B., Radyk, M. D., Redlich, N. J., Tzeng, S., Kami, K., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.077 · Cited by 160 · 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

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

Systemic Immunometabolism: Challenges and Opportunities

Lercher, A., Baazim, H., & Bergthaler, A. (2020) · Immunity · doi:10.1016/j.immuni.2020.08.012 · Cited by 141 · see citing works

Type I Interferon Signaling Disrupts the Hepatic Urea Cycle and Alters Systemic Metabolism to Suppress T Cell Function

Lercher, A., Bhattacharya, A., Popa, A., Caldera, M., Schlapansky, M. F., Baazim, H., Agerer, B., Gürtl, B., Kosack, L., Májek, P., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.10.014 · Cited by 120 · see citing works

Arginine deiminase resistance in melanoma cells is associated with metabolic reprogramming, glucose dependence, and glutamine addiction

Long, Y., Tsai, W.-B., Wangpaichitr, M., Tsukamoto, T., Savaraj, N., Feun, L. G., & Kuo, M. T. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0302 · Cited by 121 · see citing works

A role for cytosolic fumarate hydratase in urea cycle metabolism and renal neoplasia

Adam, J., Yang, M., Bauerschmidt, C., Kitagawa, M., O’Flaherty, L., Maheswaran, P., Özkan, G., Sahgal, N., Baban, D., Kato, K., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.04.006 · Cited by 97 · see citing works

A metabolic synthetic lethal strategy with arginine deprivation and chloroquine leads to cell death in ASS1-deficient sarcomas

Bean, G. R., Kremer, J. C., Prudner, B. C., Schenone, A. D., Yao, J.-C., Schultze, M., Chen, D. Y., Tanas, M. R., Adkins, D. R., Bomalaski, J. S., et al. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.232 · Cited by 97 · see citing works

Phase I Trial of Arginine Deprivation Therapy with ADI-PEG 20 Plus Docetaxel in Patients with Advanced Malignant Solid Tumors

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

Amino 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

Arginine deprivation in cancer therapy

Feun, L. G., Kuo, M. T., & Savaraj, N. (2014) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000122 · Cited by 84 · see citing works

Nitric oxide is a positive regulator of the Warburg effect in ovarian cancer cells

Caneba, C. A., Yang, L., Baddour, J., Curtis, R. N., Win, J., Hartig, S. M., Marini, J. C., & Nagrath, D. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.264 · Cited by 84 · see citing works

A Phase II Study of Arginine Deiminase (ADI-PEG20) in Relapsed/Refractory or Poor-Risk Acute Myeloid Leukemia Patients

Tsai, H., Jiang, S. S., Hung, W.-C., Borthakur, G. M., Lin, S.-F., Pemmaraju, N., Jabbour, E. J., Bomalaski, J. S., Chen, Y., Hsiao, H., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-10542-4 · Cited by 77 · see citing works

TRAIL induces autophagic protein cleavage through caspase activation in melanoma cell lines under arginine deprivation

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

A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma

Hall, 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

Down-regulation of argininosuccinate synthetase is associated with cisplatin resistance in hepatocellular carcinoma cell lines: implications for PEGylated arginine deiminase combination therapy

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

Arginine deprivation by arginine deiminase ofStreptococcus pyogenescontrols primary glioblastoma growthin vitroandin vivo

Fiedler, T., Strauß, M., Hering, S., Redanz, U., William, D., Rosche, Y., Classen, C. F., Kreikemeyer, B., Linnebacher, M., & Maletzki, C. (2015) · Cancer Biology & Therapy · doi:10.1080/15384047.2015.1026478 · Cited by 63 · 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

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

Arginine deprivation as a strategy for cancer therapy: An insight into drug design and drug combination

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

Argininosuccinate synthetase 1 (ASS1) is a common metabolic marker of chemosensitivity for targeted arginine- and glutamine-starvation therapy

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

Arginine deprivation inhibits pancreatic cancer cell migration, invasion and EMT via the down regulation of Snail, Slug, Twist, and MMP1/9

Wang, H., Li, Q., Chow, H. Y., Choi, S., & Leung, Y.-C. (2019) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-019-00716-1 · Cited by 50 · see citing works

Amino 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

Amino Acids in Cancer and Cachexia: An Integrated View

Ragni, M., Fornelli, C., Nisoli, E., & Penna, F. (2022) · Cancers · doi:10.3390/cancers14225691 · Cited by 47 · see citing works

Argininosuccinate lyase is a potential therapeutic target in breast cancer

Huang, H.-L., Chen, W.-C., Hsu, H., Cho, C.-Y., Hung, Y.-H., Wang, C., & Lai, M.-D. (2015) · Oncology Reports · doi:10.3892/or.2015.4280 · Cited by 47 · see citing works

Phase 1b study of pegylated arginine deiminase (ADI-PEG 20) plus Pembrolizumab in advanced solid cancers

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

The role of arginine and the modified arginine deiminase enzyme ADI-PEG 20 in cancer therapy with special emphasis on Phase I/II clinical trials

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

Pegylated arginine deiminase synergistically increases the cytotoxicity of gemcitabine in human pancreatic cancer

Daylami, R., Muilenburg, D. J., Virudachalam, S., & Bold, R. J. (2014) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/preaccept-8245834981349245 · Cited by 43 · see citing works

Targeting argininosuccinate synthetase negative melanomas using combination of arginine degrading enzyme and cisplatin

Savaraj, N., Wu, C., Li, Y., Wangpaichitr, M., You, M., Bomalaski, J. S., He, W., Kuo, M. T., & Feun, L. G. (2015) · Oncotarget · doi:10.18632/oncotarget.3370 · Cited by 42 · see citing works

Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment

Chu, Y., Lai, M., & Yeh, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310668 · Cited by 42 · see citing works

Arginine deiminase augments the chemosensitivity of argininosuccinate synthetase-deficient pancreatic cancer cells to gemcitabine via inhibition of NF-κB signaling

Liu, J., Ma, J., Wu, Z., Li, W., Zhang, D., Han, L., Wang, F., Reindl, K. M., Wu, E., & Ma, Q. (2014) · BMC Cancer · doi:10.1186/1471-2407-14-686 · Cited by 41 · see citing works

Phase 1 trial of ADI-PEG20 plus cisplatin in patients with pretreated metastatic melanoma or other advanced solid malignancies

Yao, S., Jankú, F., Subbiah, V., Stewart, J., Patel, S. P., Kaseb, A. O., Westin, S. N., Naing, A., Tsimberidou, A. M., Hong, D. S., et al. (2021) · British Journal of Cancer · doi:10.1038/s41416-020-01230-8 · Cited by 41 · see citing works

Integrating T cell metabolism in cancer immunotherapy

Dugnani, E., Pasquale, V., Bordignon, C., Canu, A., Piemonti, L., & Monti, P. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.09.039 · Cited by 38 · see citing works

Phase II Study of Arginine Deprivation Therapy With Pegargiminase in Patients With Relapsed Sensitive or Refractory Small-cell Lung Cancer

Hall, P. E., Ready, N., Johnston, A. L., Bomalaski, J. S., Venhaus, R. R., Sheaff, M. T., Krug, L. M., & Szlosarek, P. W. (2020) · Clinical Lung Cancer · doi:10.1016/j.cllc.2020.07.012 · Cited by 35 · see citing works

Preclinical safety and antitumor activity of the arginine-degrading therapeutic enzyme pegzilarginase, a PEGylated, cobalt-substituted recombinant human arginase 1

Agnello, G., Alters, S. E., & Rowlinson, S. W. (2019) · Translational research · doi:10.1016/j.trsl.2019.12.005 · Cited by 34 · see citing works

Bench-to-Bedside Studies of Arginine Deprivation in Cancer

Field, G., Pavlyk, I., & Szlosarek, P. W. (2023) · Molecules · doi:10.3390/molecules28052150 · Cited by 34 · see citing works

Increased expression of argininosuccinate synthetase protein predicts poor prognosis in human gastric cancer

Shan, Y., Hsu, H., Lai, M.-D., Yen, M., LUO, Y.-P., & Chen, Y. (2014) · Oncology Reports · doi:10.3892/or.2014.3556 · Cited by 33 · see citing works

The Combination of Arginine Deprivation and 5-Fluorouracil Improves Therapeutic Efficacy in Argininosuccinate Synthetase Negative Hepatocellular Carcinoma

Thongkum, A., Wu, C., Li, Y.-Y., Wangpaichitr, M., Navasumrit, P., Parnlob, V., Sricharunrat, T., Bhudhisawasdi, V., Ruchirawat, M., & Savaraj, N. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18061175 · Cited by 33 · see citing works

Synthetic lethality: a step forward for personalized medicine in cancer

Jariyal, H., Weinberg, F. D., Achreja, A., Nagarath, D., & Srivastava, A. (2019) · Drug Discovery Today · doi:10.1016/j.drudis.2019.11.014 · Cited by 30 · see citing works

L-Lysine α-Oxidase: Enzyme with Anticancer Properties

Lukasheva, E. V., Babayeva, G. A., Karshieva, S. S., Zhdanov, D. D., & Pokrovsky, V. S. (2021) · Pharmaceuticals · doi:10.3390/ph14111070 · Cited by 31 · see citing works

Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence

Murali, R., Balasubramaniam, V., Srinivas, S., Sundaram, S., Venkatraman, G., Warrier, S. R., Dharmarajan, A., & Gandhirajan, R. K. (2023) · Metabolites · doi:10.3390/metabo13040560 · Cited by 32 · see citing works

A Phase 1 study of ADI‐PEG20 (pegargiminase) combined with cisplatin and pemetrexed in ASS1‐negative metastatic uveal melanoma

Chan, P. Y., Phillips, M. M., Ellis, S. M., Johnston, A. L., Feng, X., Arora, A., Hay, G. R., Cohen, V. M. L., Sagoo, M. S., Bomalaski, J. S., et al. (2022) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.13042 · Cited by 29 · see citing works

Phase I study of ADI‐PEG20 plus low‐dose cytarabine for the treatment of acute myeloid leukemia

Tsai, H., Hsiao, H., Hsu, Y., Liu, Y., Kao, H., Liu, T., Cho, S., Feng, X., Johnston, A. L., Bomalaski, J. S., et al. (2021) · Cancer Medicine · doi:10.1002/cam4.3871 · Cited by 29 · see citing works

Improved method for expression and isolation of the Mycoplasma hominis arginine deiminase from the recombinant strain of Escherichia coli

Fayura, L. R., Boretsky, Y. R., Pynyaha, Y. V., Wheatley, D. N., & Sibirny, A. А. (2013) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2013.06.025 · Cited by 29 · see citing works

Expansion Phase 1 Study of Pegargiminase Plus Pemetrexed and Cisplatin in Patients With Argininosuccinate Synthetase 1–Deficient Mesothelioma: Safety, Efficacy, and Resistance Mechanisms

Szlosarek, P. W., Phillips, M. M., Pavlyk, I., Steele, J. P. C., Shamash, J., Spicer, J. F., Kumar, S. S., Pacey, S., Feng, X., Johnston, A. L., et al. (2020) · JTO Clinical and Research Reports · doi:10.1016/j.jtocrr.2020.100093 · Cited by 28 · see citing works

Regulated Arginine Metabolism in Immunopathogenesis of a Wide Range of Diseases: Is There a Way to Pass between Scylla and Charybdis?

Старикова, Э. А., Rubinstein, A., Mammedova, J. T., Isakov, D., & Kudryavtsev, I. V. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45040231 · Cited by 30 · see citing works

Single Amino Acid Arginine Deprivation Triggers Prosurvival Autophagic Response in Ovarian Carcinoma SKOV3

Shuvayeva, G., Bobak, Y. P., Igumentseva, N. I., Titone, R., Morani, F., Stasyk, O. V., & Isidoro, C. (2014) · BioMed Research International · doi:10.1155/2014/505041 · Cited by 27 · see citing works

Chromatin remodeling system p300-HDAC2-Sin3A is involved in Arginine Starvation-Induced HIF-1α Degradation at the ASS1 promoter for ASS1 Derepression

Tsai, W.-B., Long, Y., Chang, J. T., Savaraj, N., Feun, L. G., Jung, M., Chen, H. H. W., & Kuo, M. T. (2017) · Scientific Reports · doi:10.1038/s41598-017-11445-0 · Cited by 27 · see citing works

Microbial arginine deiminase: A multifaceted green catalyst in biomedical sciences

Kawatra, A., Dhankhar, R., & Gulati, P. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.12.015 · Cited by 26 · see citing works

Oncogenic Kaposi’s Sarcoma-Associated Herpesvirus Upregulates Argininosuccinate Synthase 1, a Rate-Limiting Enzyme of the Citrulline-Nitric Oxide Cycle, To Activate the STAT3 Pathway and Promote Growth Transformation

Li, T., Zhu, Y., Cheng, F., Lu, C., Jung, J. U., & Gao, S. (2018) · Journal of Virology · doi:10.1128/jvi.01599-18 · Cited by 26 · see citing works

Phase 1 trial of ADI‐PEG 20 and liposomal doxorubicin in patients with metastatic solid tumors

Yao, S., Jankú, F., Koenig, K. B., Tsimberidou, A. M., Piha-Paul, S. A., Shi, N., Stewart, J., Johnston, A. L., Bomalaski, J. S., Meric‐Bernstam, F., et al. (2021) · Cancer Medicine · doi:10.1002/cam4.4446 · Cited by 24 · see citing works

Dietary Manipulation of Amino Acids for Cancer Therapy

Jiménez‐Alonso, J. J., & López‐Lázaro, M. (2023) · Nutrients · doi:10.3390/nu15132879 · Cited by 24 · see citing works

Differential expression of argininosuccinate synthetase in serous and non‐serous ovarian carcinomas

Cheon, D., Walts, A. E., Beach, J. A., Lester, J., Bomalaski, J. S., Walsh, C., Wiedemeyer, W. R., Karlan, B. Y., & Oršulić, S. (2014) · The Journal of Pathology Clinical Research · doi:10.1002/cjp2.4 · Cited by 24 · see citing works

Gas6/Axl is the sensor of arginine-auxotrophic response in targeted chemotherapy with arginine-depleting agents

Tsai, W.-B., Long, Y., Park, J.-R., Chang, J. T., Liu, H., Rodriguez‐Canales, J., Savaraj, N., Feun, L. G., Davies, M. A., Wistuba, I. I., et al. (2015) · Oncogene · doi:10.1038/onc.2015.237 · Cited by 24 · see citing works

Protein Engineering of the Antitumor Enzyme PpADI for Improved Thermal Resistance

Zhu, L., Cheng, F., Piatkowski, V., & Schwaneberg, U. (2013) · ChemBioChem · doi:10.1002/cbic.201300433 · Cited by 23 · see citing works

Arginine Deiminase: Current Understanding and Applications

Zarei, M., Rahbar, M. R., Morowvat, M. H., Nezafat, N., Negahdaripour, M., Berenjian, A., & Ghasemi, Y. (2018) · Recent Patents on Biotechnology · doi:10.2174/1872208313666181220121400 · Cited by 21 · see citing works

Granulocyte functions are independent of arginine availability

Kapp, K., Prüfer, S., Michel, C. S., Habermeier, A., Luckner‐Minden, C., Giese, T., Bomalaski, J. S., Langhans, C., Kropf, P., Müller, I., et al. (2014) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ab0214-082r · Cited by 20 · see citing works

Three-dimensional environment renders cancer cells profoundly less susceptible to a single amino acid starvation

Vynnytska‐Myronovska, B., Kurlishchuk, Y. V., Bobak, Y. P., Dittfeld, C., Kunz‐Schughart, L. A., & Stasyk, O. V. (2013) · Amino Acids · doi:10.1007/s00726-013-1586-x · Cited by 18 · see citing works

Arginine Deprivation in SCLC: Mechanisms and Perspectives for Therapy

Carpentier, J., Pavlyk, I., Mukherjee, U., Hall, P. E., & Szlosarek, P. W. (2022) · Lung Cancer Targets and Therapy · doi:10.2147/lctt.s335117 · Cited by 16 · see citing works

SLC7A5 is required for cancer cell growth under arginine-limited conditions

Dunlap, K., Bender, A., Bowles, A., Bott, A. J., Tay, J., Grossmann, A. H., Rutter, J. P., & Ducker, G. S. (2025) · Cell Reports · doi:10.1016/j.celrep.2024.115130 · Cited by 16 · see citing works

Research progress on the role of cationic amino acid transporter (CAT) family members in malignant tumors and immune microenvironment

You, S., Han, X., Xu, Y., & Yao, Q. (2023) · Amino Acids · doi:10.1007/s00726-023-03313-1 · Cited by 14 · see citing works

Amino Acid Uptake Measured by [18F]AFETP Increases in Response to Arginine Starvation in ASS1-Deficient Sarcomas

Prudner, B. C., Sun, F., Kremer, J. C., Xu, J., Huang, C., Sai, K. K. S., Morgan, Z., Leeds, H., McConathy, J., & Tine, B. A. V. (2018) · Theranostics · doi:10.7150/thno.22083 · Cited by 14 · see citing works

Co-application of canavanine and irradiation uncouples anticancer potential of arginine deprivation from citrulline availability

Kurlishchuk, Y. V., Vynnytska‐Myronovska, B., Grosse‐Gehling, P., Bobak, Y. P., Manig, F., Chen, O., Merker, S. R., Henle, T., Löck, S., Stange, D. E., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.12320 · Cited by 14 · see citing works

A novel combination therapy of arginine deiminase and an arginase inhibitor targeting arginine metabolism in the tumor and immune microenvironment.

Ye, P.-H., Li, C.-Y., Cheng, H., Anuraga, G., Wang, C., Chen, F., Yang, S.-J., Lee, K., Chang, K., & Lai, M. (2023) · PubMed Central · Cited by 13 · see citing works

Evaluation of Arginine Deiminase Treatment in Melanoma Xenografts Using 18F-FLT PET

Stelter, L., Fuchs, S., Jungbluth, A. A., Ritter, G., Longo, V. A., ZANZONICO, P. B., Raschzok, N., Sauer, I. M., Bomalaski, J. S., & Larson, S. M. (2013) · Molecular Imaging and Biology · doi:10.1007/s11307-013-0655-6 · Cited by 13 · see citing works

Amino Acid Metabolic Vulnerabilities in Acute and Chronic Myeloid Leukemias

Bhingarkar, A., Vangapandu, H. V., Rathod, S., Hoshitsuki, K., & Fernandez, C. A. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.694526 · Cited by 11 · see citing works

Next generation oncolytic viruses expressing PADI1 and TIMP2 exhibit anti-tumor activity against melanoma in nude and humanized mouse models

Kuryk, Ł., & Møller, A. W. (2023) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2023.01.002 · Cited by 12 · see citing works

Enhancing the Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Signaling and Arginine Deprivation in Melanoma

Wu, C., You, M., Nguyen, D. M., Wangpaichitr, M., Li, Y., Feun, L. G., Kuo, M. T., & Savaraj, N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147628 · Cited by 12 · see citing works

Purification of a dimeric arginine deiminase from Enterococcus faecium GR7 and study of its anti-cancerous activity

Kaur, B., & Kaur, R. (2015) · Protein Expression and Purification · doi:10.1016/j.pep.2015.09.011 · Cited by 12 · see citing works

Argininosuccinate synthetase (ASS) deficiency in high-grade pulmonary neuroendocrine carcinoma: an opportunity for personalized targeted therapy

Walts, A. E., Bomalaski, J. S., Ines, D., & Oršulić, S. (2014) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-014-1904-z · Cited by 12 · see citing works

Arginine addiction in AML

Plunkett, W. K. (2015) · Blood · doi:10.1182/blood-2015-05-643411 · Cited by 12 · see citing works

Polymorphic Variants of ASS1 Gene Related to Arginine Metabolism and the Risk of HCC

Bibi, K., Fatima, T., Sohrab, S., Haider, G., Zarina, S., & Ilyas, A. (2023) · Protein and Peptide Letters · doi:10.2174/0929866530666230529143121 · Cited by 11 · see citing works

Targeting nutrient metabolism with FDA-approved drugs for cancer chemoprevention: Drugs and mechanisms

Xie, Y., Yao, K., Dong, Z., & Liu, K. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.03.029 · Cited by 8 · see citing works

Arginine Competition in Tumor Microenvironment: A Potential Target for Cancer Therapy

Zhang, J., Wang, S., Liu, H., Luo, L., & You, J. (2025) · Medicinal Research Reviews · doi:10.1002/med.70015 · Cited by 7 · see citing works

The exploitation of enzyme-based cancer immunotherapy

Chandan, G., Saini, A. K., Kumari, R., Chakrabarti, S., Mittal, A., Sharma, A. K., & Saini, R. V. (2022) · Human Cell · doi:10.1007/s13577-022-00821-2 · Cited by 7 · see citing works

Nitric oxide donor augments antineoplastic effects of arginine deprivation in human melanoma cells

Mayevska, O. M., Chen, O., Karatsai, O., Bobak, Y. P., Barska, M., Lyniv, L., Pavlyk, I., Rzhepetskyy, Y., Igumentseva, N. I., Rędowicz, M. J., et al. (2017) · Experimental Cell Research · doi:10.1016/j.yexcr.2017.04.003 · Cited by 7 · see citing works

Mono-PEGylated thermostable Bacillus caldovelox arginase mutant (BCA-M-PEG20) induces apoptosis, autophagy, cell cycle arrest and growth inhibition in gastric cancer cells

Chung, S., Tam, S.-Y., Kim, C.-F., Chong, H.-C., Lee, L. M.-Y., & Leung, Y. (2022) · Investigational New Drugs · doi:10.1007/s10637-022-01265-z · Cited by 6 · see citing works

Cancer therapies based on enzymatic amino acid depletion

Teixeira, C. S. S., Fernandes, H. S., Fernandes, P. A., Ramos, M. J., & Cerqueira, N. M. F. S. A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-46144-3.00024-6 · Cited by 6 · see citing works

Broad Anti-Cancer Activity Produced by Targeted Nutrients Deprivation (TND) of Multiple Non-Essential Amino Acids

Li, Z., Zhou, S. Y., Yang, X., Li, X., Yang, G. X., Chant, J., Snyder, M. P., & Wang, X. (2021) · Nutrition and Cancer · doi:10.1080/01635581.2021.2013904 · Cited by 6 · see citing works

Overexpression of SLC25A15 is involved in the proliferation of cutaneous melanoma and leads to poor prognosis

Ji, S.-M. (2018) · médecine/sciences · doi:10.1051/medsci/201834f113 · Cited by 5 · see citing works

Parallel Expression of Enzyme Inhibitors of CD8T Cell Activity in Tumor Microenvironments and Secretory Endometrium

Ibana, J. A., Cutay, S. J., Romero, M., & Schust, D. J. (2015) · Reproductive Sciences · doi:10.1177/1933719115602762 · Cited by 5 · see citing works

Tumor starvation by L-arginine deprivation

Fried, R., Carlton, R. M., & Fried, D. A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-824013-7.00005-5 · Cited by 2 · see citing works

Targeting Cancer Metabolism Dependencies

Harding, K. (2023) · CABI eBooks · doi:10.1079/9781789245820.0004 · Cited by 2 · see citing works

In-vivo evaluation of human recombinant Co-arginase against A375 melanoma xenografts

Agrawal, V., Woo, J. H., Mauldin, J., Stone, E. M., Meininger, C. J., Jo, C., Kleypas, K., Frenkel, E. P., & Frankel, A. E. (2014) · Melanoma Research · doi:10.1097/cmr.0000000000000119 · Cited by 2 · see citing works

Enzymes in oncohematology: relevant directions of experimental studies and prospects of clinical use

Pokrovskiy, V. S., & Трещалина, Е. М. (2014) · Clinical oncohematology · doi:10.21320/2500-2139-2014-7-1-28-38 · Cited by 2 · see citing works

Energetics of whole genome doubling and genomic instability

Beck, R. J., Tagal, V., Amin, S. B., Bakhoum, S. F., Maley, C. C., Verhaak, R. G. W., Gomes, A. P., & Andor, N. (2025) · Cancer Letters · doi:10.1016/j.canlet.2025.217878 · Cited by 1 · see citing works

Mechanisms of l-Arginine-Auxotrophic Response and Their Cancer Therapeutic Implications

Tsai, W.-B., Long, Y., Savaraj, N., Feun, L. G., & Kuo, M. T. (2016) · Springer eBooks · doi:10.1007/978-3-319-26009-9_44 · Cited by 1 · see citing works

Purification of a chemotherapeutic agent, L-Arginase, from Pseudomonas aeruginosa isolated from soil

Abd, Z. A., Abbas, Z. R., & Al-Ezee, A. M. M. (2024) · The Journal of Infection in Developing Countries · doi:10.3855/jidc.18979 · Cited by 2 · see citing works

l-Arginine in Cancer Therapy

Feun, L. G., Wangpaichitr, M., Wu, C., Li, Y., You, M., Kuo, M. T., & Savaraj, N. (2016) · Springer eBooks · doi:10.1007/978-3-319-26009-9_43

Arginine (Arg) deprivation for the treatment of advanced melanoma: Clinical results/correlation with argininosuccinate synthetase (ASS) expression

Savaraj, N., You, M., Wu, C., Marini, A., Kuo, M. T., Wangpaichitr, M., Bomalaski, J. S., & Feun, L. G. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.26.15_suppl.20019

Phase II study of pegylated arginine deiminase (ADI-PEG20), a novel targeted therapy for melanoma

Feun, L. G., Savaraj, N., Marini, A., Wu, C., Robles, C., Herrera, C., Spector, S. A., Luedemann, K., Moffat, F. L., & Bomalaski, J. S. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.24.18_suppl.8045 · Cited by 6 · see citing works

Determining argininosuccinate synthetase (ASS) expression in patients with melanoma treated with arginine depleting therapy.

Dinh, V., You, M., Savaraj, N., Wu, C., Kuo, M. T., Wangpaichitr, M., & Feun, L. G. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.29.15_suppl.10627 · Cited by 4 · see citing works

The Relationship of Arginine Deprivation, Argininosuccinate Synthetase and Cell Death in Melanoma

Savaraj, N., Wu, C., Kuo, M. T., You, M., Wangpaichitr, M., Robles, C., Spector, S. A., & Feun, L. G. (2007) · Drug Target Insights · doi:10.1177/117739280700200016 · Cited by 30 · see citing works

REVIEW

Melanoma, D. I., Savaraj, N., Wu, C., Kuo, M. T., You, M., Wangpaichitr, M., Robles, C., Spector, S., & Feun, L. (2013)