دورية أكاديمية
Comprehensive Molecular Characterization of Soft Tissue Sarcoma for Prediction of Pazopanib-Based Treatment Response
| العنوان: | Comprehensive Molecular Characterization of Soft Tissue Sarcoma for Prediction of Pazopanib-Based Treatment Response |
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| المساهمون: | Jung Yong Hong, Hee Jin Cho, Kum-Hee Yun, Young Han Lee, Seung Hyun Kim, Wooyeol Baek, Sang Kyum Kim, Yurimi Lee, Yoon-La Choi, Minsuk Kwon, Hyo Song Kim, Jeeyun Lee, Kim, Sang Kyum |
| بيانات النشر: | Official journal of Korean Cancer Association |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Humans, Indazoles / therapeutic use, Pyrimidines / pharmacology, Pyrimidines / therapeutic use, Sarcoma* / drug therapy, Sarcoma* / genetics, Sulfonamides / pharmacology, Sulfonamides / therapeutic use, Immune checkpoint inhibitors, Pazopanib, Soft tissue sarcoma, Whole exome sequencings, Whole transcriptome sequencing |
| الوصف: | Purpose Even though pazopanib, a multitargeted tyrosine kinase inhibitor, has been approved for refractory soft tissue sarcoma (STS), little is known about the molecular determinants of the response to pazopanib. We performed integrative molecular characterization to identify potential predictors of pazopanib efficacy.Materials and Methods We obtained fresh pre-treatment tumor tissue from 35 patients with advanced STS receiving pazopanib-based treatment. Among those, 18 (51.4%) received pazopanib monotherapy, and the remaining 17 (48.6%) received pazopanib in combination with durvalumab, programmed death-ligand 1 blockade. Whole-exome and transcriptome sequencing were performed for each tumor and patient germline DNA.Results Of the 35 patients receiving pazopanib-based treatment, nine achieved a partial response (PR), resulting in an objective response rate (ORR) of 27.3%, and the median progression-free survival (PFS) was 6.0 months. Patients with CDK4 amplification (copy ratio tumor to normal > 2) exhibited shorter PFS (3.7 vs. 7.9 months, p=2.09×10–4) and a poorer response (ORR; 0% vs. 33.3%) compared to those without a gene amplification (copy ratio ≤ 2). Moreover, non-responders demonstrated transcriptional activation of CDK4 via DNA amplification, resulting in cell cycle activation. In the durvalumab combination cohort, seven of the 17 patients (41.2%) achieved a PR, and gene expression analysis revealed that durvalumab responders exhibited high immune/stromal cell infiltration, mainly comprising natural killer cells, compared to non-responders as well as increased expression of CD19, a B-cell marker.Conclusion Despite the limitation of heterogeneity in the study population and treatment, we identified possible molecular predictors of pazopanib efficacy that can be employed in future clinical trials aimed at evaluating therapeutic strategies. ; open |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English Korean |
| تدمد: | 1598-2998 2005-9256 |
| العلاقة: | CANCER RESEARCH AND TREATMENT; J00453; OAK-2023-00893; OAK-2023-00894; OAK-2023-00895; OAK-2023-00896; OAK-2023-00897; https://ir.ymlib.yonsei.ac.kr/handle/22282913/194163Test; T202302505; CANCER RESEARCH AND TREATMENT, Vol.55(2) : 671-683, 2023-04 |
| DOI: | 10.4143/crt.2022.251 |
| الإتاحة: | https://doi.org/10.4143/crt.2022.251Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/194163Test |
| حقوق: | CC BY-NC-ND 2.0 KR |
| رقم الانضمام: | edsbas.B4764405 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15982998 20059256 |
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| DOI: | 10.4143/crt.2022.251 |