Phase II Study of Ganitumab, a Fully Human Anti–Type-1 Insulin-Like Growth Factor Receptor Antibody, in Patients With Metastatic Ewing Family Tumors or Desmoplastic Small Round Cell Tumors

Tap, William D.; Demetri, George D.; Barnette, Phillip; Desai, Jayesh; Kavan, Petr; Tozer, Richard; Benedetto, Pasquale; Friberg, Gregory; Deng, Hongjie; McCaffery, Ian; Leitch, Ian M.; Badola, Sunita; Chang, Sung Soo; Zhu, Min; Tolcher, Anthony W.

doi:10.1200/jco.2011.37.2359

Cited by 197 publications

(123 citation statements)

References 20 publications

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“…Phase I studies using anti-ILG R1, trabectedin, tyrosine kinase inhibitors, ganitumab, temsirolimus alone, and temsirolimus combined with cixutumumab (a fully human IgG1 monoclonal antibody directed against insulin growth factor 1 receptor, IGF-1R) have reported interesting results in this disease. [25][26][27][28][29][30] On the basis of our results, patients should receive induction chemotherapy because it may select the best candidates for surgery and improve rates of complete resection. A radiologic response was observed in 68 % of our patients.…”

Section: Discussionmentioning

confidence: 96%

Abdominal Desmoplastic Small Round Cell Tumor: Multimodal Treatment Combining Chemotherapy, Surgery, and Radiotherapy is the Best Option

et al. 2014

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Section: Discussionmentioning

confidence: 96%

Abdominal Desmoplastic Small Round Cell Tumor: Multimodal Treatment Combining Chemotherapy, Surgery, and Radiotherapy is the Best Option

et al. 2014

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“…Also, we need more effective agents for metastatic patients. There are ongoing clinical trials investigating monoclonal antibodies, small molecule inhibitors targeting the insulin like growth factor-1 receptor (Juergens et al, 2011;Tap et al, 2012;Schwartz et al, 2013). But most of them are phase I or II trials.…”

Section: Discussionmentioning

confidence: 99%

Treatment and Outcomes of Ewing Sarcoma in Turkish Adults: A Single Centre Experience

Şeker

Köş²,

Özdemir³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…S6C) that did not correlate with stage, grade, or patient survival (Supplementary Table S7). As a first approach to testing for the correlation between DVL3 protein and sensitivity to IGFIR inhibition, we assessed DVL3 in Ewing sarcomas, reported to be responsive to IGFIR inhibitor monotherapy (4,5,46,47), and head and neck squamous cell cancers (HNSCC) that are resistant (48). The results are shown in Fig.…”

Section: Dvl3 Expression In Clinical Cancersmentioning

confidence: 99%

Dsh Homolog DVL3 Mediates Resistance to IGFIR Inhibition by Regulating IGF-RAS Signaling

et al. 2014

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Drugs that inhibit insulin-like growth factor 1 (IGFI) receptor IGFIR were encouraging in early trials, but predictive biomarkers were lacking and the drugs provided insufficient benefit in unselected patients. In this study, we used genetic screening and downstream validation to identify the WNT pathway element DVL3 as a mediator of resistance to IGFIR inhibition. Sensitivity to IGFIR inhibition was enhanced specifically in vitro and in vivo by genetic or pharmacologic blockade of DVL3. In breast and prostate cancer cells, sensitization tracked with enhanced MEK-ERK activation and relied upon MEK activity and DVL3 expression. Mechanistic investigations showed that DVL3 is present in an adaptor complex that links IGFIR to RAS, which includes Shc, growth factor receptor-bound-2 (Grb2), son-of-sevenless (SOS), and the tumor suppressor DAB2. Dual DVL and DAB2 blockade synergized in activating ERKs and sensitizing cells to IGFIR inhibition, suggesting a nonredundant role for DVL3 in the Shc-Grb2-SOS complex. Clinically, tumors that responded to IGFIR inhibition contained relatively lower levels of DVL3 protein than resistant tumors, and DVL3 levels in tumors correlated inversely with progression-free survival in patients treated with IGFIR antibodies. Because IGFIR does not contain activating mutations analogous to EGFR variants associated with response to EGFR inhibitors, we suggest that IGF signaling achieves an equivalent integration at the postreceptor level through adaptor protein complexes, influencing cellular dependence on the IGF axis and identifying a patient population with potential to benefit from IGFIR inhibition. Cancer Res; 74(20); 5866-77. Ó2014 AACR.

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Phase II Study of Ganitumab, a Fully Human Anti–Type-1 Insulin-Like Growth Factor Receptor Antibody, in Patients With Metastatic Ewing Family Tumors or Desmoplastic Small Round Cell Tumors

Abstract: Ganitumab was well tolerated and demonstrated antitumor activity in patients with advanced recurrent EFT or DSRCT.

Cited by 197 publications

References 20 publications

Abdominal Desmoplastic Small Round Cell Tumor: Multimodal Treatment Combining Chemotherapy, Surgery, and Radiotherapy is the Best Option

Abdominal Desmoplastic Small Round Cell Tumor: Multimodal Treatment Combining Chemotherapy, Surgery, and Radiotherapy is the Best Option

Treatment and Outcomes of Ewing Sarcoma in Turkish Adults: A Single Centre Experience

Dsh Homolog DVL3 Mediates Resistance to IGFIR Inhibition by Regulating IGF-RAS Signaling

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