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:Recent advances in immune-based approaches for the treatment of esophagogastric cancer.
免疫治疗,特别是免疫检查点抑制剂(ICI)类药物类别的引入,近年来改变了许多癌症的治疗范式。抗PD-1疗法现已成为局部和晚期疾病患者的新标准治疗。
2021年将被铭记为食管癌和胃癌治疗领域的变革之年。数十年来失败的临床试验使得治疗进展仅限于对传统综合治疗模式的改进。针对特定分子改变的靶向策略——除Her2外——未能带来所期望的突破,而基于免疫的方法能为这类癌症带来什么尚不清楚。食管胃癌中TIL(肿瘤浸润淋巴细胞)的存在表明内源性免疫反应已经发生,并可能通过免疫检查点抑制被放大。近期数据已通过FDA在局部区域疾病(CheckMate 577)和转移性疾病(CheckMate 649、KeyNote 590和KeyNote 811)中的批准验证了这一点,这些批准改变了治疗格局。涵盖领域:在此我们讨论近期数据和正在进行的研究工作,以更好地界定基于免疫方法的作用,并筛选出可能从中获益最多的患者群体。
INTRODUCTION: The year 2021 will be remembered as a transformational year in the management of both esophageal and gastric cancers. Decades of failed clinical trials had seen limited therapeutic advances beyond refinement of the traditional combined modality approach. Targeted strategies against specific molecular alterations did not - with the exception of Her2 - yield the desired breakthroughs, and it was unclear what immune-based approaches would bring to this group of cancers. The presence of tumor-infiltrating lymphocytes in esophagogastric cancer demonstrates that an endogenous immune response is already occurring and potentially amplifiable by immune checkpoint inhibition. Recent data have validated this with FDA approvals in both the locoregional (CheckMate 577) and metastatic disease (CheckMate 649, KeyNote 590 and KeyNote 811) setting which have altered the therapeutic landscape. AREAS COVERED: Here we discuss recent data and ongoing research efforts to better define the role of immune-based approaches and select the patient cohorts who might gain the most benefit from them. EXPERT OPINION: Immunotherapy, and specifically the incorporation of the immune checkpoint inhibitors (ICI) drug class, has altered the therapeutic paradigm of many cancers in recent years. Anti-PD-1 therapies are now the new standard of care for patients with local and advanced disease.
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