التفاصيل البيبلوغرافية
| العنوان: |
IGF-1R/mTOR Targeted Therapy for Ewing Sarcoma: A Meta-Analysis of Five IGF-1R-Related Trials Matched to Proteomic and Radiologic Predictive Biomarkers. |
| المؤلفون: |
Amin, Hesham M., Morani, Ajaykumar C., Daw, Najat C., Lamhamedi-Cherradi, Salah-Eddine, Subbiah, Vivek, Menegaz, Brian A., Vishwamitra, Deeksha, Eskandari, Ghazaleh, George, Bhawana, Benjamin, Robert S., Patel, Shreyaskumar, Song, Juhee, Lazar, Alexander J., Wang, Wei-Lien, Kurzrock, Razelle, Pappo, Alberto, Anderson, Peter M., Schwartz, Gary K., Araujo, Dejka, Cuglievan, Branko |
| المصدر: |
Cancers; Jul2020, Vol. 12 Issue 7, p1768, 1p |
| مصطلحات موضوعية: |
ANTINEOPLASTIC agents, THERAPEUTIC use of monoclonal antibodies, CANCER treatment, CELL receptors, COMPUTED tomography, DEOXY sugars, GLYCOLYSIS, META-analysis, OSTEOSARCOMA, RADIOPHARMACEUTICALS, SURVIVAL analysis (Biometry), POSITRON emission tomography, TRANSFERASES, TUMOR markers, PROTEOMICS, SPECIALTY hospitals, TREATMENT effectiveness, SIGNAL peptides, DESCRIPTIVE statistics, CHEMICAL inhibitors |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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