Department of Lymphoma/Myeloma, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Nat Rev Clin Oncol. 2012 Nov;9(11):643-53. doi: 10.1038/nrclinonc.2012.156. Epub 2012 Sep 11.
Over the past three decades, the pathological classification of lymphoma has substantially improved. The early Rappaport classification included a handful of subtypes that did not reflect the cell of origin and, not surprisingly, resulted in diagnostic inaccuracies. The WHO currently classifies lymphoma into 30 major distinctive types. While this classification improved the accuracy and consistency of the histological diagnosis of lymphoma, it had little impact on advancing drug development or improving the cure rate of this disease. One reason for this lack of improvement is that recent developments in cancer genomics show these histopathological subtypes to be heterogeneous. Basing treatment decisions on histopathological subtypes is inefficient as it groups different underlying molecular characteristics into one category. Such a strategy exposes many patients to potentially toxic drugs without providing benefits. The recent approval of two new cancer drugs with companion diagnostics to allow selection and treatment of patients with melanoma and non-small-cell lung cancer has raised hope that a similar approach may also expedite successful drug development in lymphoma. We review the current status of biomarker development in lymphoma, and discuss novel biomarker-directed clinical trial designs for lymphoma.
在过去的三十年中，淋巴瘤的病理学分类有了实质性的改进。早期的 Rappaport 分类包括少数几种不能反映起源细胞的亚型，毫不奇怪，这导致了诊断不准确。目前，世界卫生组织（WHO）将淋巴瘤分为 30 种主要独特类型。虽然这种分类提高了淋巴瘤组织学诊断的准确性和一致性，但对推进药物开发或提高这种疾病的治愈率影响甚微。造成这种缺乏改善的原因之一是，癌症基因组学的最新发展表明这些组织病理学亚型存在异质性。基于组织病理学亚型做出治疗决策效率低下，因为它将不同的潜在分子特征归入一个类别。这种策略使许多患者面临潜在的毒性药物，而没有带来益处。最近批准了两种新的癌症药物，并附有伴随诊断，以允许选择和治疗黑色素瘤和非小细胞肺癌患者，这让人们希望类似的方法也可能加速淋巴瘤的成功药物开发。我们回顾了淋巴瘤生物标志物开发的现状，并讨论了针对淋巴瘤的新型生物标志物指导的临床试验设计。
