{"doi":"10.3390/cancers12071768","title":"IGF-1R/mTOR Targeted Therapy for Ewing Sarcoma: A Meta-Analysis of Five IGF-1R-Related Trials Matched to Proteomic and Radiologic Predictive Biomarkers","abstract":"Background : Ten to fourteen percent of Ewing sarcoma (ES) study participants treated nationwide with IGF-1 receptor (IGF-1R)-targeted antibodies achieved tumor regression. Despite this success, low response rates and short response durations (approximately 7-weeks) have slowed the development of this therapy. Methods: We performed a meta-analysis of five phase-1b/2 ES-oriented trials that evaluated the anticancer activity of IGF-1R antibodies +/− mTOR inhibitors (mTORi). Our meta-analysis provided a head-to-head comparison of the clinical benefits of IGF-1R antibodies vs. the IGF-1R/mTOR-targeted combination. Available pretreatment clinical samples were semi-quantitatively scored using immunohistochemistry to detect proteins in the IGF-1R/PI3K/AKT/mTOR pathway linked to clinical response. Early PET/CT imaging, obtained within the first 2 weeks (median 10 days), were examined to determine if reduced FDG avidity was predictive of progression-free survival (PFS). Results: Among 56 ES patients treated at MD Anderson Cancer Center (MDACC) with IGF-1R antibodies, our analysis revealed a significant ~two-fold improvement in PFS that favored a combination of IGF-1R/mTORi therapy (1.6 vs. 3.3-months, p = 0.042). Low pIGF-1R in the pretreatment specimens was associated with treatment response. Reduced total-lesion glycolysis more accurately predicted the IGF-1R response than other previously reported radiological biomarkers. Conclusion: Synergistic drug combinations, and newly identified proteomic or radiological biomarkers of IGF-1R response, may be incorporated into future IGF-1R-related trials to improve the response rate in ES patients.","journal":"Cancers","year":2020,"id":95399,"datarank":0.5416376868966337,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":0.0,"self_endowment_contribution":0.5416376868966337,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.963,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":473839,"name":"Ajaykumar C. Morani","orcid":"0000-0002-2936-0291","position":1,"is_corresponding":false},{"id":473840,"name":"Najat C. Daw","orcid":"0000-0002-6941-8005","position":2,"is_corresponding":false},{"id":473841,"name":"Salah-Eddine Lamhamedi-Cherradi","orcid":"0000-0002-8324-4769","position":3,"is_corresponding":false},{"id":226642,"name":"Vivek Subbiah","orcid":"0000-0002-6064-6837","position":4,"is_corresponding":false},{"id":473842,"name":"Brian A. Menegaz","orcid":"0000-0002-3020-5790","position":5,"is_corresponding":false},{"id":474440,"name":"Deeksha Vishwamitra","orcid":null,"position":6,"is_corresponding":false},{"id":265116,"name":"Ghazaleh Eskandari","orcid":null,"position":7,"is_corresponding":false},{"id":295628,"name":"Bhawana George","orcid":"0000-0002-7528-0452","position":8,"is_corresponding":false},{"id":473843,"name":"Robert S. Benjamin","orcid":"0000-0002-2589-5870","position":9,"is_corresponding":false},{"id":260061,"name":"Shreyaskumar Patel","orcid":"0000-0002-0026-2348","position":10,"is_corresponding":false},{"id":291127,"name":"Juhee Song","orcid":"0000-0002-8688-4104","position":11,"is_corresponding":false},{"id":13708,"name":"Alexander J. Lazar","orcid":"0000-0002-6395-4499","position":12,"is_corresponding":false},{"id":473844,"name":"Wei Wang","orcid":"0009-0006-8927-8990","position":13,"is_corresponding":false},{"id":108759,"name":"Razelle Kurzrock","orcid":"0000-0003-4110-1214","position":14,"is_corresponding":false},{"id":267020,"name":"Alberto S. Pappo","orcid":"0000-0002-5338-3979","position":15,"is_corresponding":false},{"id":465977,"name":"Peter M. Anderson","orcid":"0000-0002-0011-0969","position":16,"is_corresponding":false},{"id":241729,"name":"Gary K. Schwartz","orcid":"0000-0003-1813-5061","position":17,"is_corresponding":false},{"id":469205,"name":"Dejka M. Araujo","orcid":"0000-0002-1223-6542","position":18,"is_corresponding":false},{"id":473845,"name":"Branko Cuglievan","orcid":"0000-0002-6917-2244","position":19,"is_corresponding":false},{"id":473846,"name":"Ravin Ratan","orcid":"0000-0002-4914-7922","position":20,"is_corresponding":false},{"id":473847,"name":"David McCall","orcid":"0000-0003-2297-9670","position":21,"is_corresponding":false},{"id":473848,"name":"Sana Mohiuddin","orcid":"0000-0003-3149-2506","position":22,"is_corresponding":false},{"id":374607,"name":"J. Andrew Livingston","orcid":"0000-0002-1337-3282","position":23,"is_corresponding":false},{"id":473849,"name":"Eric R. Molina","orcid":"0000-0003-2662-3524","position":24,"is_corresponding":false},{"id":266105,"name":"Aung Naing","orcid":"0000-0002-4803-8513","position":25,"is_corresponding":false},{"id":473850,"name":"Joseph A. Ludwig","orcid":"0000-0001-6631-8554","position":26,"is_corresponding":false},{"id":473838,"name":"Hesham M. Amin","orcid":"0000-0002-7973-6699","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:33:30.364261Z","pmid":"32630797","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}