Mismatch Repair Deficiency and Response to Immune Checkpoint Blockade
Mismatch Repair Deficiency and Response to Immune Checkpoint Blockade
复制标题
DOI：
10.1634/theoncologist.2016-0046
复制
发表时间：
2016-10-01
期刊：
影响因子：
5.8
通讯作者：
Diaz, Luis A., Jr.
中科院分区：
文献类型：
--
作者：
Lee, Valerie;Murphy, Adrian;Diaz, Luis A., Jr.
2016年，美国将诊断出超过160万例新的癌症病例，导致超过50万人死亡。尽管化疗一直是晚期癌症治疗的主要手段，但免疫疗法的发展，特别是PD-1抑制剂的发展，已经改变了许多肿瘤类型的治疗面貌。一个例子是以错配修复缺陷和微卫星不稳定性为特征的肿瘤子集，其对PD-1阻断高度敏感。癌症的遗传形式已经被注意到超过一个世纪，但直到20世纪90年代初才知道错配修复缺陷肿瘤和随后的微卫星不稳定肿瘤的分子变化。在这篇综述文章中，我们讨论了错配修复的历史和病理生理学，错配修复缺陷和微卫星不稳定性的检测过程，以及免疫治疗在这类癌症中的作用。
More than 1.6 million new cases of cancer will be diagnosed in the U.S. in 2016, resulting in more than 500,000 deaths. Although chemotherapy has been the mainstay of treatment in advanced cancers, immunotherapy development, particularly with PD-1 inhibitors, has changed the face of treatment for a number of tumor types. One example is the subset of tumors characterized by mismatch repair deficiency and microsatellite instability that are highly sensitive to PD-1 blockade. Hereditary forms of cancer have been noted for more than a century, but the molecular changes underlying mismatch repair-deficient tumors and subsequent microsatellite unstable tumors was not known until the early 1990s. In this review article, we discuss the history and pathophysiology of mismatch repair, the process of testing for mismatch repair deficiency and microsatellite instability, and the role of immunotherapy in this subset of cancers.