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 a study of cixutumab plus temsirolimus in 10 patients with ACC, stable disease in 4 patients, at a maximum lasting greater than 8 months, was the best response.
“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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“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 · see citing works
“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 · see citing works
“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 · see citing works
“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 48 · see citing works
Faes, S., Santoro, T., Demartines, N., & Dormond, O. (2017) · Cancers · doi:10.3390/cancers9110152 · Cited by 47 · see citing works
Andersson, M. K., Åman, P., & Stenman, G. (2019) · Cells · doi:10.3390/cells8080913 · Cited by 44 · see citing works
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 43 · see citing works
“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 42 · see citing works
“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 · see citing works
“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 40 · see citing works
“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 · see citing works
“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 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
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 37 · see citing works
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 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
“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 35 · see citing works
“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 · see citing works
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 · see citing works
Szurián, K., Kashofer, K., & Liegl‐Atzwanger, B. (2017) · Pathobiology · doi:10.1159/000478662 · Cited by 34 · see citing works
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 · see citing works
“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 · see citing works
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 · see citing works
“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 · see citing works
“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 · see citing works
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 · see citing works
“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 30 · see citing works
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 · see citing works
“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 28 · see citing works
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 28 · see citing works
“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 · see citing works
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 27 · see citing works
“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 27 · see citing works
“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 · see citing works
“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 · see citing works
“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 · see citing works
Ewing's sarcoma: overcoming the therapeutic plateau.
Subbiah, V., & Kurzrock, R. (2012) · PubMed · Cited by 26 · see citing works
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 · see citing works
“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 26 · see citing works
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 · see citing works
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 · see citing works
“[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 · see citing works
“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 · see citing works
“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 · see citing works
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 · see citing works
Chen, H., & Feng, G. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s190333 · Cited by 23 · see citing works
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 · see citing works
“[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 · see citing works
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 · see citing works
Zhao, Q., Tran, H., Dimitrov, D. S., & Cheung, N. V. (2015) · International Journal of Cancer · doi:10.1002/ijc.29588 · Cited by 22 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
- 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 › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › 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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