Department of Surgery, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Front Med. 2018 Apr;12(2):229-235. doi: 10.1007/s11684-017-0581-0. Epub 2017 Dec 5.
On May 23, 2017, the US Food and Drug Administration (FDA) approved a treatment for cancer patients with positive microsatellite instability-high (MSI-H) markers or mismatch repair deficient (dMMR) markers. This approach is the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body. FDA previously approved Keytruda for treatment of several types of malignancies, such as metastatic melanoma, metastatic non-small-cell lung cancer, recurrent or metastatic head and neck cancer, refractory Hodgkin lymphoma, and urothelial carcinoma, all of which carry positive programmed death-1/programmed death-ligand 1 biomarkers. Therefore, indications of Keytruda significantly expanded. Several types of malignancies are disclosed by MSI-H status due to dMMR and characterized by increased neoantigen load, which elicits intense host immune response in tumor microenvironment, including portions of colorectal and gastric carcinomas. Currently, biomarker-based patient selection remains a challenge. Pathologists play important roles in evaluating histology and biomarker results and establishing detection methods. Taking gastric cancer as an example, its molecular classification is built on genome abnormalities, but it lacks acceptable clinical characteristics. Pathologists are expected to act as "genetic interpreters" or "genetic translators" and build a link between molecular subtypes with tumor histological features. Subsequently, by using their findings, oncologists will carry out targeted therapy based on molecular classification.
2017 年 5 月 23 日,美国食品和药物管理局(FDA)批准了一种用于治疗微卫星不稳定性高(MSI-H)标志物或错配修复缺陷(dMMR)标志物阳性的癌症患者的治疗方法。这种方法是第一种使用常见生物标志物而非体内特定肿瘤部位批准的肿瘤治疗方法。FDA 此前已批准 Keytruda 用于治疗多种恶性肿瘤,如转移性黑色素瘤、转移性非小细胞肺癌、复发性或转移性头颈部癌、难治性霍奇金淋巴瘤和尿路上皮癌,所有这些都带有阳性程序性死亡-1/程序性死亡配体 1 生物标志物。因此,Keytruda 的适应证显著扩大。由于 dMMR 导致 MSI-H 状态的几种类型的恶性肿瘤,其特征是新抗原负荷增加,在肿瘤微环境中引发强烈的宿主免疫反应,包括部分结直肠癌和胃癌。目前,基于生物标志物的患者选择仍然是一个挑战。病理学家在评估组织学和生物标志物结果以及建立检测方法方面发挥着重要作用。以胃癌为例,其分子分类建立在基因组异常的基础上,但缺乏可接受的临床特征。病理学家有望充当“遗传解释器”或“遗传翻译器”,在分子亚型与肿瘤组织学特征之间建立联系。随后,肿瘤学家将根据分子分类进行靶向治疗。