Genomics, Morphoproteomics, and Treatment Patterns of Patients with Alveolar Soft Part Sarcoma and Response to Multiple Experimental Therapies
| العنوان: | Genomics, Morphoproteomics, and Treatment Patterns of Patients with Alveolar Soft Part Sarcoma and Response to Multiple Experimental Therapies |
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| المؤلفون: | Alexander J. Lazar, Roman Groisberg, Vivek Subbiah, Robert E. Brown, Daniella E Portal, Aung Naing, Neeta Somaiah, Maria Alejandra Zarzour, Cynthia E. Herzog, Jason Roszik, Anthony P. Conley, David S. Hong, Shreyaskumar Patel |
| المصدر: | Mol Cancer Ther |
| بيانات النشر: | American Association for Cancer Research (AACR), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Cancer Research, Adolescent, Proteome, medicine.drug_class, Genomics, medicine.disease_cause, Article, Tyrosine-kinase inhibitor, Young Adult, 03 medical and health sciences, 0302 clinical medicine, CDKN2A, Alveolar soft part sarcoma, Biomarkers, Tumor, Humans, Medicine, Immune Checkpoint Inhibitors, Protein Kinase Inhibitors, Retrospective Studies, Mutation, business.industry, Standard treatment, Prognosis, medicine.disease, Gene Expression Regulation, Neoplastic, Clinical trial, Sarcoma, Alveolar Soft Part, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, Female, Hepatocyte growth factor, business, Follow-Up Studies, medicine.drug |
| الوصف: | Overexpression of transcription factor 3 in alveolar soft part sarcoma(ASPS) results in upregulation of cell proliferation pathways. No standard treatment algorithm exists for ASPS; multikinase inhibitors[tyrosine kinase inhibitor (TKI)] and immune checkpoint inhibitors (ICI) have shown clinical benefit. To date, no studies have reported on management strategies or sequencing of therapy. We evaluated ASPS treatment patterns and responses in an experimental therapeutics clinic. Genomic and morphoproteomic analysis was performed to further elucidate novel targets. We retrospectively reviewed patients with ASPS treated on clinical trials. Demographic and clinical next-generation sequencing (NGS) profiles were collected. AACR GENIE database was queried to further evaluate aberrations in ASPS. Morphoproteomic analysis was carried out to better define the biology of ASPS with integration of genomic and proteomic findings. Eleven patients with ASPS were identified; 7 received NGS testing and mutations in CDKN2A (n = 1) and hepatocyte growth factor (n = 1) were present. Ten patients were treated with TKIs with stable disease as best response and 4 patients with ICI (three partial responses). Within GENIE, 20 patients were identified harboring 3 called pathogenic mutations. Tumor mutation burden was low in all samples. Morphoproteomic analysis confirmed the expression of phosphorylated c-Met. In addition, fatty acid synthase and phosphorylated-STAT3 were detected in tumor cell cytoplasm and nuclei. Patients with ASPS have a quiescent genome and derive clinical benefit from VEGF-targeting TKIs. Morphoproteomic analysis has provided both additional correlative pathways and angiogenic mechanisms that are targetable for patients with ASPS. Our study suggests that sequential therapy with TKIs and immune checkpoint inhibitors is a reasonable management strategy. |
| تدمد: | 1538-8514 1535-7163 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::582f252d4fbd9619909bd4bff53ac144 https://doi.org/10.1158/1535-7163.mct-19-0579 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....582f252d4fbd9619909bd4bff53ac144 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15388514 15357163 |
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