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:Immunotherapy and Biomarkers in Sarcoma.
传统化疗或抗血管生成药物治疗带来的缓解不持久,生存率约为12至18个月。
肉瘤是一组罕见且异质性的疾病。目前转移性肉瘤的治疗选择相当有限。常规化疗或抗血管生成药物治疗导致非持久缓解,生存率约为12至18个月。此外,此类治疗的获益仅局限于某些肉瘤亚型。免疫治疗是多种癌症类型的新兴治疗方法,具有前景良好的结果。细胞水平的研究显示,某些肉瘤亚型具有相对较高的免疫原性。因此,推测肉瘤可能对免疫治疗有反应。然而,肉瘤是一种异质性疾病,在免疫原性方面存在差异。已探索了多种针对肉瘤的免疫治疗方法。这包括免疫检查点抑制剂、治疗性疫苗和过继细胞治疗。单药免疫治疗已显示出对某些肉瘤亚型的疗效,包括腺泡状软组织肉瘤、血管肉瘤和未分化多形性肉瘤。在缓解方面,联合免疫治疗似乎优于单药免疫治疗,并且多项正在进行的免疫治疗研究使用单药/联合免疫检查点抑制剂以及与抗血管生成联合,已开始报告有益结果。预测性和预后性生物标志物也正在积极研究中,特别关注TIL(肿瘤浸润淋巴细胞)或高肿瘤突变负荷水平。然而,信息仍然有限,需要进一步研究。
Sarcoma describes a rare and heterogeneous group of diseases. Current treatment options for metastatic sarcoma are quite limited. Conventional treatments with chemotherapy or anti-angiogenic agents result in a non-durable response and a survival rate of approximately 12 to 18 months. In addition, the benefits of such treatments remain limited in some sarcoma subtypes only. Immunotherapy is an emerging treatment for several cancer types with promising outcomes. Studies at the cellular level have shown a relatively high immunogenicity in some subtypes of sarcoma. It is therefore hypothesized that sarcoma may respond to immunotherapy. However, sarcoma is a heterogeneous disease and differences in terms of immunogenicity exist. A multitude of immune-based treatment approaches for sarcoma have been explored. This includes immune checkpoint inhibitors, therapeutic vaccines, and adoptive cell therapy. Single-agent immunotherapy has exhibited efficacy against some sarcoma subtypes, including alveolar soft-part sarcoma, angiosarcoma, and undifferentiated pleomorphic sarcoma. Combination immunotherapy appears superior to single-agent immunotherapy in terms of response, and several ongoing studies of immunotherapy using single/combination immune checkpoint inhibitors and combination with anti-angiogenesis have begun to report beneficial results. Predictive and prognostic biomarkers are also under active investigations, with particular interest in tumor-infiltrating lymphocytes or high tumor mutational burden levels. However, the information is still limited and further studies are needed.
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