下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Emerging targeted and cellular therapies in the treatment of advanced and metastatic synovial sarcoma.
Emerging targeted and cellular therapies in the treatment of advanced and metastatic synovial sarcoma.
滑膜肉瘤是一种软组织肉瘤,在美国每年约有1,000例病例。
滑膜肉瘤是一种软组织肉瘤,在美国每年约有1,000例。目前,晚期和转移性滑膜肉瘤的标准治疗是蒽环类为基础的化疗。虽然晚期滑膜肉瘤相比其他软组织肉瘤对化疗更敏感,但生存率较差,中位生存时间不到18个月。对滑膜肉瘤肿瘤抗原表达和分子机制的深入理解提供了潜在的治疗靶点。使用工程化T细胞受体的过继细胞转移正在临床试验中用于治疗滑膜肉瘤,具体靶向纽约食管鳞状细胞癌-1(NY-ESO-1)、黑色素瘤优先表达抗原(PRAME)和黑色素瘤抗原-A4(MAGE-A4)。在这篇综述中,我们探讨了这些治疗的机遇和挑战。我们还描述了人工佐剂载体细胞(aAVCs)和BRD9抑制剂,这两个额外的潜在治疗晚期滑膜肉瘤的靶点。这篇综述展示了滑膜肉瘤治疗方面取得的进展,并强调了将这些技术作为标准治疗实施所需的未来研究和资质认证。
Synovial sarcoma is a soft tissue sarcoma accounting for approximately 1,000 cases per year in the United States. Currently, standard treatment of advanced and metastatic synovial sarcoma is anthracycline-based chemotherapy. While advanced synovial sarcoma is more responsive to chemotherapy compared to other soft tissue sarcomas, survival rates are poor, with a median survival time of less than 18 months. Enhanced understanding of tumor antigen expression and molecular mechanisms behind synovial sarcoma provide potential targets for treatment. Adoptive Cell Transfer using engineered T-cell receptors is in clinical trials for treatment of synovial sarcoma, specifically targeting New York esophageal squamous cell carcinoma-1 (NY-ESO-1), preferentially expressed antigen in melanoma (PRAME), and melanoma antigen-A4 (MAGE-A4). In this review, we explore the opportunities and challenges of these treatments. We also describe artificial adjuvant vector cells (aAVCs) and BRD9 inhibitors, two additional potential targets for treatment of advanced synovial sarcoma. This review demonstrates the progress that has been made in treatment of synovial sarcoma and highlights the future study and qualification needed to implement these technologies as standard of care.
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