Department of Internal Medicine, Indiana University, Indianapolis, IN, USA.
Department of Pathology, Beaumont Labs, Beaumont Health, Royal Oak, MI, USA.
Ann Clin Lab Sci. 2021 Jul;51(4):461-469.
Chemotherapy originated in the early 1960s. The initial chemotherapeutic agents focused on blocking metabolic pathways and found substantial success in certain types of tumors, but they are generally considered toxic to all normal and tumor cells, and they have significant side effects. As more scientific studies began to identify many new, specific targets and mutations, along with a multitude of growth pathways in tumor cells, new agents targeting cell growth pathways began to emerge in the late 1990s and early 2000s. In 2003, a method called morphoproteomics was developed to evaluate the immunohistochemical protein expressions of target markers in tumors, and it has been considered a pioneering method for guiding targeted therapy. Subsequently, many genomic techniques have been established for identifying specific mutations and tumor markers in order to guide the targeted therapy. More recently, immuno-oncology therapy targeting specific immune markers has been rapidly developed, and the immunohistochemical evaluation of specific immune markers such as PD-L1 demonstrates further expansion of oncologic morphoproteomics. This brief review will focus on the role of pathologists in developing various techniques and guiding targeted therapies during the era of personalized medicine.
化疗起源于 20 世纪 60 年代初。最初的化疗药物侧重于阻断代谢途径,在某些类型的肿瘤中取得了显著的成功,但它们通常被认为对所有正常和肿瘤细胞都有毒性,并且具有显著的副作用。随着越来越多的科学研究开始识别许多新的、特定的靶点和突变,以及肿瘤细胞中大量的生长途径,新的靶向细胞生长途径的药物在 20 世纪 90 年代末和 21 世纪初开始出现。2003 年,开发了一种称为形态蛋白质组学的方法来评估肿瘤中目标标志物的免疫组织化学蛋白表达,它被认为是指导靶向治疗的开创性方法。随后,建立了许多基因组技术来识别特定的突变和肿瘤标志物,以指导靶向治疗。最近,针对特定免疫标志物的免疫肿瘤治疗得到了迅速发展,对 PD-L1 等特定免疫标志物的免疫组织化学评估进一步扩展了肿瘤形态蛋白质组学。这篇简短的综述将重点介绍病理学家在个性化医疗时代开发各种技术和指导靶向治疗中的作用。