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Insulin Growth Factor-Receptor (IGF-1R) Antibody Cixutumumab Combined with the mTOR Inhibitor Temsirolimus in Patients with Refractory Ewing's Sarcoma Family Tumors
Open accessAbstract
PURPOSE: Temsirolimus was combined with cixutumumab, a fully human IgG1 monoclonal antibody directed at the insulin growth factor-1 receptor (IGF-1R). EXPERIMENTAL DESIGN: Patients received cixutumumab, 6 mg/kg i.v. weekly, and temsirolimus, 25 to 37.5 mg i.v. weekly (4-week cycles), with restaging after 8 weeks. Median follow-up was 8.9 months. RESULTS: Twenty patients [17 with Ewing's sarcoma (EWS), 3 with desmoplastic small-round cell tumor (DSRCT)] were enrolled. Twelve patients (60%) were men with a median age of 24 years and six median prior systemic therapies in a metastatic setting. The most frequent toxicities were thrombocytopenia (85%), mucositis (80%), hypercholesterolemia (75%), hypertriglyceridemia (70%), and hyperglycemia (65%; mostly grade I-II). Seven of 20 patients (35%) achieved stable disease (SD) for more than 5 months or complete/partial (CR/PR) responses. Tumor regression of more than 20% (23%, 23%, 27%, 100%, 100%) occurred in five of 17 (29%) patients with EWS, and they remained on study for 8 to 27 months. One of six patients with EWS who previously developed resistance to a different IGF-1R inhibitor antibody achieved a CR. Four of the seven best responders developed grade III mucositis, myelosuppression, or hyperglycemia, which were controlled while maintaining drug dose. CONCLUSION: Cixutumumab combined with temsirolimus was well-tolerated and showed preliminary evidence of durable antitumor activity in heavily pretreated EWS family tumors.
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“In another study, cixutumab in combination with temsirolimus was evaluated in 10 patients with ACC. Stable disease in 4 patients, at a maximum lasting for greater than 8 months, was the best response (317).”
From Adrenocortical carcinoma (2014) · cites this paper as [317]
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1 retracted
Shi, Y., Yan, H., Frost, P., Gera, J., & Lichtenstein, A. K. (2005) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-05-0068 · Cited by 368
RetractedNew Guidelines to Evaluate the Response to Treatment in Solid Tumors
Therasse, P., Arbuck, S. G., Eisenhauer, E. A., Wanders, J., Kaplan, R. S., Rubinstein, L., Verweij, J., Van Glabbeke, M., van Oosterom, A. T., Christian, M. C., et al. (2000) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/92.3.205 · Cited by 15,660
SEER Cancer Statistics Review, 1975-2003
Ries, L. A. G., Harkins, D., Krapcho, M. F., Mariotto, A. B., Miller, B., Feuer, E. J., Clegg, L. X., Eisner, M. P., Horner, M., Howlader, N., et al. (2006) · Digital Archive @ GSU · Cited by 11,404
Targeting the phosphoinositide 3-kinase pathway in cancer
Liu, P., Cheng, H.-L. M., Roberts, T. M., & Zhao, J. J. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2926 · Cited by 2,785
mTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt
O'Reilly, K. E., Rojo, F., She, Q.-B., Solit, D., Mills, G. B., Smith, D., Lane, H., Hofmann, F., Hicklin, D. J., Ludwig, D. L., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2925 · Cited by 2,561
Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism
Wan, X., Harkavy, B., Shen, N., Grohar, P. J., & Helman, L. J. (2006) · Oncogene · doi:10.1038/sj.onc.1209990 · Cited by 761
Balamuth, N., & Womer, R. B. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70286-4 · Cited by 727
Prieur, A., Tirode, F., Cohen, P., & Delattre, O. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.16.7275-7283.2004 · Cited by 427 · cited 1×
“EWS–FLI can bind the IGFBP3 promoter and repress its activity, further supporting the role of IGF-1R signaling in this malignancy (19).”
Olmos, D., Postel-Vinay, S. C., Molife, L. R., Okuno, S. H., Schuetze, S. M., Paccagnella, M. L., Batzel, G. N., Yin, D., Pritchard‐Jones, K., Judson, I. R., et al. (2009) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70354-7 · Cited by 339
Tolcher, A. W., Sarantopoulos, J., Patnaik, A., Papadopoulos, K. P., Lin, C., Rodon, J. A., Murphy, B. A., Roth, B. J., McCaffery, I., Gorski, K. S., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.23.6745 · Cited by 306
Cited by
Sorted by citations
Else, T., Kim, A. C., Sabolch, A., Raymond, V. M., Kandathil, A., Caoili, E. M., Jolly, S., Miller, B. S., Giordano, T. J., & Hammer, G. D. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1029 · Cited by 892
Ewing Sarcoma—Diagnosis, Treatment, Clinical Challenges and Future Perspectives
Zöllner, S. K., Amatruda, J. F., Bauer, S., Collaud, S., de Álava, E., DuBois, S. G., Hardes, J., Hartmann, W., Kovar, H., Metzler, M., et al. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10081685 · Cited by 292
Modeling Ewing sarcoma tumors in vitro with 3D scaffolds
Fong, E. L. S., Lamhamedi-Cherradi, S.-E., Burdett, E., Ramamoorthy, V., Lazar, A. J., Kasper, F. K., Farach‐Carson, M. C., Vishwamitra, D., Demicco, E. G., Menegaz, B. A., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1221403110 · Cited by 238
“Despite a wealth of preclinical information and two recent clinical trials demonstrating marked tumor regression in a subset of patients with EWS treated with combined antagonists of the IGF-1R/mTOR pathway, we noted a surprising lackluster cellular response to IGF-1R antagonists in conventional 2D monolayer culture (…”
BackgroundSingh, P., Alex, J. M., & Bast, F. (2013) · Medical Oncology · doi:10.1007/s12032-013-0805-3 · Cited by 208
“A series of conventional drugs such as Temsirolimus were combined with cixutumumab, a fully human IgG1 monoclonal antibody intended to target IGF-1R resulted in antitumor activity against Ewing’s family tumors without side effects [133].”
BackgroundIGF-1R as an anti-cancer target--trials and tribulations
Chen, H. X., & Sharon, E. (2013) · 癌症：英文版 · doi:10.5732/cjc.012.10263 · Cited by 202
Schwartz, G. K., Tap, W. D., Qin, L., Livingston, M. B., Undevia, S. D., Chmielowski, B., Agulnik, M., Schuetze, S. M., Reed, D. R., Okuno, S. H., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70049-4 · Cited by 187
Iams, W. T., & Lovly, C. M. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2518 · Cited by 180
“The combination ofmTOR inhibitionwith IGF1R inhibition in patients with advanced sarcoma has yielded results similar to those from IGF1R monotherapy (19, 30, 36, 43, 44), and the combination of IGF1R inhibition with cytotoxic chemotherapy has yielded provocative results in patients with leiomyosarcoma (18, 45).”
BackgroundResultInfluentialInsulin-like Growth Factor Receptor Inhibitors: Baby or the Bathwater?
Yee, D. (2012) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djs258 · Cited by 177
“Early reports suggest that this combination of IGF1R and mTOR inhibition has clinical benefits in Ewing’s sarcoma (53).”
BackgroundBowers, L. W., Rossi, E. L., Oâ€TMFlanagan, C. H., deGraffenried, L. A., & Hursting, S. D. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00077 · Cited by 186
Toxicity of targeted therapy: Implications for response and impact of genetic polymorphisms
Liu, S., & Kurzrock, R. (2014) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2014.05.003 · Cited by 166
“some metabolic toxicities [81] [78–81] 84”
Trial Watch: Monoclonal antibodies in cancer therapy
Galluzzi, L., Vacchelli, E., Fridman, W. H., Galon, J., Sautès‐Fridman, C., Tartour, É., Zucman‐Rossi, J., Zitvogel, L., & Kroemer, G. (2012) · OncoImmunology · doi:10.4161/onci.1.1.17938 · Cited by 152
A review of soft-tissue sarcomas: translation of biological advances into treatment measures
Hoang, N. T., Acevedo, L. A., Mann, M. J., & Tolani, B. (2018) · Cancer Management and Research · doi:10.2147/cmar.s159641 · Cited by 141
Yin, Y., Hua, H. M., Li, M., Liu, S., Kong, Q., Shao, T., Wang, J., Luo, Y., Wang, Q., Luo, T. L., et al. (2015) · Cell Research · doi:10.1038/cr.2015.133 · Cited by 147
Naing, A., LoRusso, P. M., Fu, S., Hong, D. S., Chen, H. X., Doyle, L. A., Phan, A. T., Habra, M. A., & Kurzrock, R. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.46 · Cited by 134
“A total of 26 patients (13 men) with advanced metastatic and/or refractory ACC were enrolled on the study.”
BackgroundInfluentialCan we unlock the potential of IGF-1R inhibition in cancer therapy?
King, H., Aleksic, T., Haluska, P., & Macaulay, V. M. (2014) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2014.07.004 · Cited by 135
“adrenocortical cancers and sarcomas including EWS [70,72,149,150], findings that clearly merit further follow-up.”
BackgroundNovel Therapeutic Approaches in Chondrosarcoma
Polychronidou, G., Karavasilis, V., Pollack, S. M., Huang, P. H., Lee, A. P., & Jones, R. L. (2017) · Future Oncology · doi:10.2217/fon-2016-0226 · Cited by 124
Targeting the insulin-like growth factor-1 receptor in human cancer
Arcaro, A. (2013) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00030 · Cited by 122
“IMC-A12 was evaluated in combination with the mammalian target of rapamycin (mTOR) inhibitor temsirolimus in patients with refractory Ewing’s sarcoma family tumors (Naing et al., 2012).”
BackgroundMethodWagner, L. M., Fouladi, M., Ahmed, A. A., Krailo, M., Weigel, B. J., DuBois, S. G., Doyle, L. A., Chen, H., & Blaney, S. M. (2014) · Pediatric Blood & Cancer · doi:10.1002/pbc.25334 · Cited by 114
“In another adult phase II trial, 2 (12%) of 17 Ewing sarcoma patients achieved complete responses, and three others had tumor reduction of >20% [13].”
BackgroundMethodInfluentialChang, W., Lin, R., Yu, J., Chang, W., Fu, C.-H., Lai, A. C., Yu, A. L.-T., & Yu, A. L.-T. (2013) · Breast Cancer Research · doi:10.1186/bcr3423 · Cited by 108
“Also, combination of IGF-1R and mTOR inhibition showed clinical benefits in Ewing’s sarcoma [52].”
Management of recurrent Ewing sarcoma: challenges and approaches
Mater, D. V., & Wagner, L. M. (2019) · OncoTargets and Therapy · doi:10.2147/ott.s170585 · Cited by 110
Subbiah, V., Lamhamedi-Cherradi, S.-E., Cuglievan, B., Menegaz, B. A., Camacho, P. E., Huh, W. W., Ramamoorthy, V., Anderson, P. M., Pollock, R. E., Lev, D. C., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0202 · Cited by 106
“Other biological therapies, including anti-ganglioside GD2 antibodies (29, 30), imatinib (31), mTOR inhibitors (32, 33), and a combination of insulin-like growth factor 1 and mTOR inhibitors (34), have shown limited success.”
BackgroundHonoré, C., Amroun, K., Vilcot, L., Mir, O., Dômont, J., Terrier, P., Cesne, A. L., Pechoux, C. L., & Bonvalot, S. (2014) · Annals of Surgical Oncology · doi:10.1245/s10434-014-4123-6 · Cited by 104
Fitzgerald, J. B., Johnson, B. W., Baum, J., Adams, S., Iadevaia, S., Tang, J., Rimkunas, V. M., Xu, L., Kohli, N., Rennard, R., et al. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0255 · Cited by 106
“Combinations of IGF-IR and mTOR inhibitors are being tested in the clinic (47); however, AKTormTOR inhibition has been shown to increase both IGF-IR and ErbB3 levels”
BackgroundAnderson, P. M., Bielack, S., Gorlick, R. G., Skubitz, K. M., Daw, N. C., Herzog, C. E., Monge, O. R., Lassaletta, Á., Boldrini, É., Pápai, Z., et al. (2016) · Pediatric Blood & Cancer · doi:10.1002/pbc.26087 · Cited by 95
“Patients with any≥Grade 3 treatment-emergent AE 16 (47) 10 (30) 14 (41) 67 (58) 107 (50)”
Vacchelli, E., Eggermont, A. M. M., Galon, J., Sautès‐Fridman, C., Zitvogel, L., Kroemer, G., & Galluzzi, L. (2012) · OncoImmunology · doi:10.4161/onci.22789 · Cited by 97
Schöffski, P., Adkins, D., Blay, J., Gil, T., ELIAS, A. D., Rutkowski, P. L., Pennock, G. K., Youssoufian, H., Gelderblom, H. A. J., Willey, R., et al. (2013) · European Journal of Cancer · doi:10.1016/j.ejca.2013.06.010 · Cited by 89
Advances in paediatric cancer treatment.
Saletta, F., Seng, M. S.-F., & Lau, L. M. S. (2014) · PubMed Central · doi:10.3978/j.issn.2224-4336.2014.02.01 · Cited by 89
Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy
de Mello, C. A. L., Campos, F. A. B., Santos, T. G., Silva, M. L. G., Torrezan, G. T., Costa, F. D., Formiga, M. N., Nicolau, U. R., Nascimento, A. G., Silva, C., et al. (2021) · Cancers · doi:10.3390/cancers13030498 · Cited by 79
“A phase I trial evaluated the combination of cixutumumab (an IGFR antibody) with temsirolimus, which resulted in stable disease lasting longer than 5 months in two of the three patients with DSRCT of the study[102].”
BackgroundWong, H. H., Hatcher, H. M., Benson, C., Al‐Muderis, O., Horan, G., Fisher, C., Earl, H. M., & Judson, I. R. (2013) · Clinical Sarcoma Research · doi:10.1186/2045-3329-3-14 · Cited by 72
“In a phase I study of another anti-IGF-1R antibody cixutumumab in combination with temsirolimus, two out of three patients with previously-treated DSRCT had SD lasting longer than 5 months [34].”
BackgroundLee, H. J., Kim, S. R., Oh, Y., Cho, S., Schleimer, R. P., & Lee, Y. C. (2013) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2013-0397tr · Cited by 72
Insulin-like growth factor — Oestradiol crosstalk and mammary gland tumourigenesis
Hawsawi, Y. M., El-Gendy, R., Twelves, C., Speirs, V., & Beattie, J. M. (2013) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2013.10.005 · Cited by 69
Ho, A. L., Vasudeva, S. D., Lae, M. E., Saito, T., Barbashina, V., Antonescu, C. R., Ladanyi, M., & Schwartz, G. K. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1319 · Cited by 65
“Exogenous growth factors are necessary for rapamycininduced Akt activation in both Class I and Class II synovial sarcoma cell lines Although susceptibility to IGF-1R targeting in rhabdomyosarcoma cell lines has been directly correlated to receptor expression levels (28), IGF-1R independence in this panel was observed…”
InfluentialBulbul, A., Fahy, B. N., Xiu, J., Rashad, S., Mustafa, A., Husain, H., & Hayes-Jordan, A. A. (2017) · Sarcoma · doi:10.1155/2017/1278268 · Cited by 68
Kovar, H. (2014) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2014.947963 · Cited by 68
Apatinib for advanced sarcoma: results from multiple institutions’ off-label use in China
Xie, L., Guo, W., Wang, Y., Yan, T., Ji, T., & Xu, J. H. (2018) · BMC Cancer · doi:10.1186/s12885-018-4303-z · Cited by 64
Lamhamedi-Cherradi, S.-E., Menegaz, B. A., Ramamoorthy, V., Vishwamitra, D., Wang, Y., Maywald, R. L., Buford, A. S., Fokt, I., Skóra, S., Wang, J., et al. (2016) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djw182 · Cited by 64
“, for example, demonstrated compelling clinical activity in adult ES patients (27).”
BackgroundResultInfluentialCrompton, B. D., Carlton, A. L., Thorner, A. R., Christie, A. L., Du, J., Calicchio, M. L., Rivera, M. N., Fleming, M. D., Kohl, N. E., Kung, A. L., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-1944 · Cited by 58
“An RNAi screen in Ewing sarcoma determined that downregulation of the mTOR pathway sensitized Ewing sarcoma cells to IGF1R inhibition, and a recent phase I study showed tumor responses in a subset of patients with refractory Ewing sarcoma using IGF1R- and mTOR-targeted combination therapy (45, 46).”
Desmoplastic Small Round Cell Tumor 20 Years After its Discovery
Mora, J., Modak, S. I., Cheung, N. V., Meyers, P. A., de Álava, E., Kushner, B. H., Magnan, H., Tirado, Ò. M., LaQuaglia, M. P., Ladanyi, M., et al. (2015) · Future Oncology · doi:10.2217/fon.15.32 · Cited by 60
Pazopanib in advanced desmoplastic small round cell tumours: a multi-institutional experience
Frezza, A. M., Benson, C., Judson, I. R., Litière, S., Marreaud, S. I., Sleijfer, S., Blay, J., Dewji, R., Fisher, C., van der Graaf, W., et al. (2014) · Clinical Sarcoma Research · doi:10.1186/2045-3329-4-7 · Cited by 59
Potential approaches to the treatment of Ewing's sarcoma
Yu, H., Ge, Y., Guo, L., & Huang, L. (2016) · Oncotarget · doi:10.18632/oncotarget.12566 · Cited by 55
“mTOR inhibitors have been more effective in combination with other agents, such as IGF1R inhibitors [22, 24, 112, 113].”
BackgroundClinical Observations and Molecular Variables of Primary Vascular Leiomyosarcoma
Roland, C. L., Boland, G. M., Demicco, E. G., Lusby, K., Ingram, D. R., May, C. D., Kivlin, C. M., Watson, K. L., Sannaa, G. A. A., Wang, W., et al. (2015) · JAMA Surgery · doi:10.1001/jamasurg.2015.4205 · Cited by 53
“(%) Patients With Localized vLMS (n = 63) TMA Patients With vLMS (n = 26) Age at diagnosis, median (range), y 58 (22-78) 55 (22-77)”
Unraveling the IGF System Interactome in Sarcomas Exploits Novel Therapeutic Options
Mancarella, C., Morrione, A., & Scotlandi, K. (2021) · Cells · doi:10.3390/cells10082075 · Cited by 52
“In addition, the combination of the anti-IGF1R mAb cixutumumab with the mTOR inhibitor temsirolimus resulted in stable disease for two of three desmoplastic small round cell tumor patients for at least 5 months [170].”
BackgroundProspects and challenges for the development of new therapies for Ewing sarcoma
Grohar, P. J., & Helman, L. J. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.10.004 · Cited by 51
“combined the IGF-1R inhibitor cixutumumab with temsirolimus found tumor regressions in 30% of Ewing sarcoma patients treated with this combination including a complete response in a patient previously refractory to IGF-1R targeting (Naing et al., 2012).”
BackgroundTemsirolimus: a safety and efficacy review
Bukowski, R. (2012) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2012.713344 · Cited by 42
“Phase I trials utilizing temsirolimus with either perifosine in neuroblastoma [81] or an insulin growth factor-receptor antibody (cixutumumab) in refractory Ewing’s sarcoma patients [82] have been reported.”
BackgroundClinical Activity of Pazopanib in Patients with Advanced Desmoplastic Small Round Cell Tumor
Menegaz, B. A., Cuglievan, B., Benson, J. A., Camacho, P. E., Lamhamedi-Cherradi, S.-E., Leung, C. H., Warneke, C. L., Huh, W. W., Subbiah, V., Benjamin, R. S., et al. (2017) · The Oncologist · doi:10.1634/theoncologist.2017-0408 · Cited by 50
“As an example, striking tumor regression occurs in approximately 10%–14% of ES patients who receive IGF-1R-targeted therapies, whereas the response in DSRCT appears more subdued in the limited data that exist [15].”
BackgroundGarofalo, C., Capristo, M., Manara, M. C., Mancarella, C., Landuzzi, L., Belfiore, A., Lollini, P., Picci, P., & Scotlandi, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083832 · Cited by 49
“activity in heavily pretreated EWS family tumors [55].”
BackgroundKoppenhafer, S. L., Goss, K. L., Terry, W. W., & Gordon, D. J. (2018) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-0260 · Cited by 50
Faes, S., Santoro, T., Demartines, N., & Dormond, O. (2017) · Cancers · doi:10.3390/cancers9110152 · Cited by 48
Andersson, M. K., Åman, P., & Stenman, G. (2019) · Cells · doi:10.3390/cells8080913 · Cited by 45
Lamhamedi-Cherradi, S.-E., Menegaz, B. A., Ramamoorthy, V., Aiyer, R. A., Maywald, R. L., Buford, A. S., Doolittle, D. K., Culotta, K. S., O'Dorisio, J. E., & Ludwig, J. A. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0334 · Cited by 45
“Therapies targeting the insulin-like growth factor 1 receptor (IGFIR), alone or in combination with inhibitors of mammalian target of rapamycin (mTOR), provide just one example of selective biologically targeted therapies capable of inducing striking tumor regression among a subset of Ewing sarcoma patients (12, 13).”
Backgroundvan Maldegem, A. M., Bovée, J. V. M. G., Peterse, E., Hogendoorn, P. C. W., & Gelderblom, H. A. J. (2016) · European Journal of Cancer · doi:10.1016/j.ejca.2015.09.009 · Cited by 43
“Tap [61] II Ganitumumab 12 mg/kg/3 week Naing [62] II Cixutumumab and Temsirolimus 6 mg/kg/week and 25 mg/kg/week”
BackgroundGamie, Z., Kapriniotis, K., Papanikolaou, D., Haagensen, E., Da Conceicao Ribeiro, R., Dalgarno, K., Krippner-Heidenreich, A., Gerrand, C., Tsiridis, E., & Rankin, K. S. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.08.036 · Cited by 44
“Turning these findings into clinical outcomes remains a challenge, although some very promising clinical trials with factors targeting the IGF pathway have been published [16].”
Novel Secondary Somatic Mutations in Ewing's Sarcoma and Desmoplastic Small Round Cell Tumors
Jiang, Y., Subbiah, V., Jankú, F., Ludwig, J. A., Naing, A., Benjamin, R. S., Brown, R. E., Anderson, P. M., & Kurzrock, R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093676 · Cited by 41
“Of interest, both of the patients with GRB10 mutations (cases #2 and #3, Table 1) responded to therapy with an IGF1R plus mTOR inhibitor and both achieved a complete remission (CR) [10].”
BackgroundAnderson, J. L., Park, A., Akiyama, R., Tap, W. D., Denny, C. T., & Federman, N. C. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133610 · Cited by 40
“In a phase I study investigating the combination of the IGF1R antibody cixutmumuab and the mTOR inhibitor temsirolimus, an ES patient that developed resistance to a different IGF1R inhibitor achieved a complete response with combination therapy [31].”
BackgroundTargeting the IGF1R/PI3K/AKT Pathway Sensitizes Ewing Sarcoma to BET Bromodomain Inhibitors
Loganathan, S. N., Tang, N., Holler, A. E., Wang, N., & Wang, J. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-1151 · Cited by 39
“A673 is an unusual Ewing sarcoma cell line that carries a BRAF mutation (36).”
BackgroundInfluentialRonchi, C. L., Kroiß, M., Sbiera, S., Deutschbein, T., & Faßnacht, M. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0273 · Cited by 39
Understanding Toxicities of Targeted Agents: Implications for Anti-tumor Activity and Management
Liu, S., & Kurzrock, R. (2015) · Seminars in Oncology · doi:10.1053/j.seminoncol.2015.09.032 · Cited by 38
Precision Oncology in Sarcomas: Divide and Conquer
Pestana, R. C., Groisberg, R., Roszik, J., & Subbiah, V. (2019) · JCO Precision Oncology · doi:10.1200/po.18.00247 · Cited by 36
Modeling the Tumor Microenvironment and Pathogenic Signaling in Bone Sarcoma
Molina, E. R., Chim, L. K., Barrios, S., Ludwig, J. A., & Mikos, A. G. (2020) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2019.0302 · Cited by 38
Mini-Review on Targeted Treatment of Desmoplastic Small Round Cell Tumor
Bexelius, T. S., Wasti, A., & Chisholm, J. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00518 · Cited by 37
“temsirolimus 20 (3) 2 SD for 5-6 months IGF-1R inhibitor and mTOR inhibition (42)”
BackgroundResponse of refractory Ewing sarcoma to pazopanib
Alcindor, T. (2014) · Acta Oncologica · doi:10.3109/0284186x.2014.971938 · Cited by 36
PTEN Deficiency Mediates a Reciprocal Response to IGFI and mTOR Inhibition
Patel, M., Gomez, N. C., McFadden, A. W., Moats‐Staats, B. M., Wu, S. B., Muñoz-Rojas, A. R., Sapp, T., Simon, J. M., Smith, S. V., Kaiser‐Rogers, K. A., et al. (2014) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-14-0006 · Cited by 36
Amin, H. M., Morani, A. C., Daw, N. C., Lamhamedi-Cherradi, S.-E., Subbiah, V., Menegaz, B. A., Vishwamitra, D., Eskandari, G., George, B., Benjamin, R. S., et al. (2020) · Cancers · doi:10.3390/cancers12071768 · Cited by 35
“in 2012, demonstrated nearly a 29% response rate and 7-fold longer median response duration (>14 months) in ES patients [25].”
BackgroundResultInfluentialExploiting Signaling Pathways and Immune Targets Beyond the Standard of Care for Ewing Sarcoma
Casey, D. L., Lin, T.-Y., & Cheung, N. V. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00537 · Cited by 38
“For ES specifically, the combination of ganitumab with rapamycin showed efficacy in preclinical modes (113), and the combination of cixutumumab and temsirolimus in the phase I setting for patients with refractory ES showed durable tumor regression in 29% of patients (114).”
BackgroundHendricks, A., Boerner, K., Germer, C., & Wiegering, A. (2020) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2020.102140 · Cited by 34
Targeting bone metastatic cancer: Role of the mTOR pathway
Bertoldo, F., Silvestris, F., Ibrahim, T., Cognetti, F., Generali, D., Ripamonti, C. I., Amadori, D., Colleoni, M. A., Conte, P., Mastro, L. D., et al. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.01.009 · Cited by 34
Szurián, K., Kashofer, K., & Liegl‐Atzwanger, B. (2017) · Pathobiology · doi:10.1159/000478662 · Cited by 34
Targeted therapies for advanced Ewing sarcoma family of tumors
Jiang, Y., Ludwig, J. A., & Jankú, F. (2015) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2015.03.008 · Cited by 31
“For example, anti-IGF1R therapies may lead to activation of downstream pathways and thus result in tumor drug resistance through a bypass pathway [26,57].”
BackgroundInfluentialMcHugh, D. J., Chudow, J., DeNunzio, M., Slovin, S. F., Danila, D. C., Morris, M. J., Scher, H. I., & Rathkopf, D. E. (2020) · Clinical Genitourinary Cancer · doi:10.1016/j.clgc.2019.10.013 · Cited by 31
Targeted siRNA nanocarrier: a platform technology for cancer treatment
Bäumer, N., Tiemann, J., Scheller, A., Meyer, T., Wittmann, L., Suburu, M. E. G., Greune, L., Peipp, M., Kellmann, N., Gumnior, A., et al. (2022) · Oncogene · doi:10.1038/s41388-022-02241-w · Cited by 31
“MATERIALS AND METHODS siRNA-carrier construction For expression of anti-IGF1R-antibodies, published sequences of the heavy chain and light of cixutumumab (“A12”[15]) and teprotumumab (“Tepro”[16]) were cloned into the bicistronic expression vector pVITRO-neo, preceded by a rituximab leader sequence and followed by an…”
MethodAdvances in Therapy for Pediatric Sarcomas
Weiss, A. R., Gill, J. B., Goldberg, J., Lagmay, J., Spraker‐Perlman, H. L., Venkatramani, R., & Reed, D. R. (2014) · Current Oncology Reports · doi:10.1007/s11912-014-0395-z · Cited by 28
“Anti-IGF-1R antibodies have been usedwith mammalian target of rapamycin (mTOR) inhibitors in refractory pediatric patients (as IGF-1R inhibition may block the potential upregulation of Akt seen with mTORmonotherapy [57]), with a few complete responses and sustained stable disease [58, 59].”
BackgroundMolina, E. R., Chim, L. K., Salazar, M. C., Koons, G. L., Menegaz, B. A., Ruiz-Velasco, A., Lamhamedi-Cherradi, S.-E., Vetter, A. M., Satish, T., Cuglievan, B., et al. (2019) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.9b01068 · Cited by 29
Germline PTPRD Mutations in Ewing Sarcoma: Biologic and Clinical Implications
Jiang, Y., Jankú, F., Subbiah, V., Angelo, L. S., Naing, A., Anderson, P. M., Herzog, C. E., Fu, S., Benjamin, R. S., & Kurzrock, R. (2013) · Oncotarget · doi:10.18632/oncotarget.1021 · Cited by 29
“Patient 1 had durable CRs resulting from IGF-1R inhibitor-based therapies (Figure 2).[14, 17-20] PBMCs from an additional seven patients (2 to 8, Table 1) with advanced Ewing sarcoma were analyzed for PTPRD germline mutations in all 35 exons (exons 11-45, ENST00000381196) using Sanger sequencing, as previously describ…”
MethodIntrinsic Resistance to Cixutumumab Is Conferred by Distinct Isoforms of the Insulin Receptor
Forest, A., Amatulli, M., Ludwig, D. L., Damoci, C. B., Wang, Y., Burns, C. A., Donoho, G. P., Zanella, N., Fiebig, H., Prewett, M. C., et al. (2015) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-15-0279 · Cited by 31
Molecular targeted therapy for advanced or metastatic soft tissue sarcoma
Yuan, J., Li, X., & Yu, S. (2021) · Cancer Control · doi:10.1177/10732748211038424 · Cited by 29
“Cixutumumab showed an unsatisfactory result in patients with EWS, but showed a significant beneficial efficacy in combination with temsirolimus, and the expression of IGF-1R may indicate the clinical benefit.(40,51,94) Apatinib was reported to have an objective response rate(ORR) of 70% in Ewing sarcoma, with median d…”
BackgroundLin, E. H., Lenz, H., Saleh, M. N., MacKenzie, M. J., Knost, J. A., Pathiraja, K., Langdon, R. B., Yao, S., & Lu, B. D. (2014) · Cancer Medicine · doi:10.1002/cam4.263 · Cited by 27
New Strategies in Ewing Sarcoma: Lost in Translation?
Arnaldez, F. I., & Helman, L. J. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0633 · Cited by 30
“A recent trial combining cixutumumab with temsiroliumus reported that 35% patients had SD longer than 5 months orCR/PR (40).”
Mancarella, C., & Scotlandi, K. (2017) · Journal of Molecular Endocrinology · doi:10.1530/jme-17-0250 · Cited by 28
Therapy resistance mechanisms in Ewing’s sarcoma family tumors
Ahmed, A. A., Zia, H. M., & Wagner, L. M. (2014) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-014-2392-1 · Cited by 30
“this hypothesis is supported by the observation that the combined targeting of IGF-1R and mtOR results in sustained complete responses in sarcoma xenografts, but has only modest clinical activity in presumably more complex and heterogeneous ewing’s sarcoma tumors [59, 60].”
ResultBone Sarcomas: From Biology to Targeted Therapies
Gaspar, N., Giannatale, A. D., Geoerger, B., Rédiní, F., Corradini, N., Entz‐Werlé, N., Tirode, F., Marec‐Bérard, P., Gentet, J., Laurence, V., et al. (2012) · Sarcoma · doi:10.1155/2012/301975 · Cited by 28
“An adult phase I combination of the anti-IGF1-R antibody cixutumumab and temsirolimus showed good tolerance and tumour regression of more than 20% in 5/17 (29%) EW patients who remained on study for 8 to 27 months, with a CR in 1/6 of EW patients who previously developed resistance to a different IGF-1R inhibitor anti…”
BackgroundNew drugs and combinations for the treatment of soft-tissue sarcoma: a review
von Mehren, M., & Somaiah (2012) · Cancer Management and Research · doi:10.2147/cmar.s23257 · Cited by 26
“5 mg IV weekly in 4-week cycles, in heavily pretreated patients with the Ewing family of tumors.(89) This was well tolerated, with preliminary evidence of durable antitumor activity.”
Zhong, H., Fazenbaker, C. A., Breen, S., Chen, C., Huang, J., Morehouse, C. A., Yao, Y., & Hollingsworth, R. E. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0144 · Cited by 26
“The results of early clinical trials revealed that combining IGFIR and mTORi has some clinical benefits in Ewing sarcoma (39).”
BackgroundChallenges of Systemic Therapy Investigations for Bone Sarcomas
Nakano, K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073540 · Cited by 25
Ewing's sarcoma: overcoming the therapeutic plateau.
Subbiah, V., & Kurzrock, R. (2012) · PubMed · Cited by 26
Prognostic and therapeutic relevance of the IGF pathway in Ewing’s sarcoma patients
van de Luijtgaarden, A. C. M., Versleijen‐Jonkers, Y. M. H., Roeffen, M. H. S., Schreuder, H. W. B., Flucke, U. E., & van der Graaf, W. T. A. (2013) · Targeted Oncology · doi:10.1007/s11523-012-0248-3 · Cited by 26
“This is consistent with evidence of enhanced efficacy of combined IGF-1R and mTOR inhibition [25, 29, 43, 46] and a combination of IGF-1R, PI3K and MEK inhibition [7].”
BackgroundTargeting the IGF/PI3K/mTOR pathway and AXL/YAP1/TAZ pathways in primary bone cancer
Truong, D. D., Lamhamedi-Cherradi, S.-E., & Ludwig, J. A. (2022) · Journal of bone oncology · doi:10.1016/j.jbo.2022.100419 · Cited by 27
New Systemic Therapy Options for Advanced Sarcomas
van der Graaf, W. T. A., & Gelderblom, H. A. J. (2012) · Current Treatment Options in Oncology · doi:10.1007/s11864-012-0196-2 · Cited by 25
Livingston, J. A., Hess, K. R., Naing, A., Hong, D. S., PATEL, S. R., Benjamin, R. S., Ludwig, J. A., Conley, A. P., Herzog, C. E., Anderson, P. M., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.10910 · Cited by 25
“[28-30] The major limitations of this study included its inclusion of patients with late-stage cancer, the referral bias inherent to phase I trials conducted in tertiary care centers, and the fact that patients received heterogeneous therapies.”
BackgroundBétrian, S., Bergeron, C., Blay, J., Bompas, E., Cassier, P. A., Chevallier, L., Fayette, J., Girodet, M., Guillemet, C., Cesne, A. L., et al. (2017) · Clinical Sarcoma Research · doi:10.1186/s13569-017-0076-4 · Cited by 25
“Based on Ewing sarcoma model and EWS-Fli translocation, leading to dysregulation of insulin growth factor 1 (IGF1) receptor and dependence on IGF1 [28, 29], humanized monoclonal antagonist IGF1 receptor (IGF1R) antibodies have been developed [30, 31].”
Vincristine, Ifosfamide, and Doxorubicin for Initial Treatment of Ewing Sarcoma in Adults
Wagner, M. J., Gopalakrishnan, V., Ravi, V., Livingston, J. A., Conley, A. P., Araujo, D. M., Somaiah, N., Zarzour, M. A., Ratan, R., Wang, W., et al. (2017) · The Oncologist · doi:10.1634/theoncologist.2016-0464 · Cited by 25
“The addition of inhibitors of the mamallian target of rapamycin yielded a clinical benefit rate of 29%, with a median duration of benefit for more than a year [18, 19].”
BackgroundO’Neill, A., Shah, N., Zitomersky, N. L., Ladanyi, M., Shukla, N. N., Üren, A., Loeb, D. M., & Toretsky, J. A. (2013) · Sarcoma · doi:10.1155/2013/450478 · Cited by 24
Fouladi, M., Perentesis, J. P., Wagner, L. M., Vinks, A. A. T. M. M., Reid, J. M., Ahern, C. H., Thomas, G., Mercer, C. A., Krueger, D. A., Houghton, P. J., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0595 · Cited by 24
Chen, H., & Feng, G. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s190333 · Cited by 23
Desmoplastic small round cell tumor: from state of the art to future clinical prospects
Hovsepyan, S., Giani, C., Pasquali, S., Giannatale, A. D., Chiaravalli, S., Colombo, C., Orbach, D. H., Bergamaschi, L., Vennarini, S., Gatz, S. A., et al. (2023) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2023.2200171 · Cited by 23
“[66] irinotecan + vincristine (plus radiotherapy) 1 patient with PR, 26 months of PFS Irinotecan and trabectidin Ferrari et al, 2022 [77] trabectidin + irinotecan: 2 patients, 1 with CR, 1 with SD Temsirolimus Thijs et al, 2010 [78] 1 patient with SD, 9 months of PFS Naing et al, 2012 [79] temsirolimus + cixutumumab:…”
BackgroundFrappaz, D., Federico, S. M., Pearson, A. D. J., Gore, L., Macy, M. E., DuBois, S. G., Aerts, I., Iannone, R., Geschwindt, R. D., van Schanke, A., et al. (2016) · European Journal of Cancer · doi:10.1016/j.ejca.2016.03.084 · Cited by 23
Chemotherapy for Bone Sarcomas in Adults: The MD Anderson Experience
Benjamin, R. S., Wagner, M. J., Livingston, J. A., Ravi, V., & PATEL, S. R. (2015) · American Society of Clinical Oncology Educational Book · doi:10.14694/edbook_am.2015.35.e656 · Cited by 22
Zhao, Q., Tran, H., Dimitrov, D. S., & Cheung, N. V. (2015) · International Journal of Cancer · doi:10.1002/ijc.29588 · Cited by 22
Nakai, S., Yamada, S., Outani, H., Nakai, T., Yasuda, N., Mae, H., Imura, Y., Wakamatsu, T., Tamiya, H., Tanaka, T., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-52143-3 · Cited by 22
Inhibition of insulin-like growth factor receptor: end of a targeted therapy?
Pillai, R. N., & Ramalingam, S. S. (2013) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2218-6751.2012.11.05 · Cited by 21
The Role of Inflammation in Sarcoma
Radons, J. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-3-0348-0837-8_11 · Cited by 22
Metadata
- Authors
- Naing, A., LoRusso, P., Fu, S., Hong, D. S., Anderson, P., Benjamin, R. S., Ludwig, J., Chen, H. X., Doyle, L. A., & Kurzrock, R.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Naing, Aung
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2012-04-30
- Volume
- 18
- Issue
- 9
- Pages
- 2625-2631
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC3875297
- OpenAlex
- W1991236371
- Cited by
- 205
- References
- 26
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7 · 2023: 5 · 2022: 7 · 2021: 15 · 2020: 10 · 2019: 10 · 2018: 9 · 2017: 12 · 2016: 15 · 2015: 27 · 2014: 31 · 2013: 31 · 2012: 13
- FWCI
- 26.32
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (U01-CA62487, U01 CA 62461, R21-CA13763301A1, U01CA062487, R21CA137633, U01CA062461, P30CA016672)
- Topics
- Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Hematology › Acute Lymphoblastic Leukemia research
- Keywords
- cixutumumab, temsirolimus, mTOR inhibitors, Ewing sarcoma, desmoplastic small round cell tumor, refractory cancer, combination therapy, hyperglycemia, mucositis, thrombocytopenia, anticancer activity
- MeSH terms
- Adolescent, Adult, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Bone Neoplasms, Female, Humans, Male, Prognosis, Remission Induction, Sarcoma, Ewing, Cohort Studies, Receptor, IGF Type 1, Sirolimus, Young Adult, Desmoplastic Small Round Cell Tumor, TOR Serine-Threonine Kinases, Neoplasm Grading, Antibodies, Monoclonal, Humanized
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