Lymphoma Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 330, New York, NY 10065, USA.
Nat Rev Clin Oncol. 2014 Oct;11(10):585-96. doi: 10.1038/nrclinonc.2014.137. Epub 2014 Aug 19.
Modern advances in genomics and cancer biology have produced an unprecedented body of knowledge regarding the molecular pathogenesis of lymphoma. The diverse histological subtypes of lymphoma are molecularly heterogeneous, and most likely arise from distinct oncogenic mechanisms. In parallel to these advances in lymphoma biology, several new classes of molecularly targeted agents have been developed with varying degrees of efficacy across the different types of lymphoma. In general, the development of new drugs for treating lymphoma has been mostly empiric, with a limited knowledge of the molecular target, its involvement in the disease, and the effect of the drug on the target. Thus, the variability observed in clinical responses likely results from underlying molecular heterogeneity. In the era of personalized medicine, the challenge for the treatment of patients with lymphoma will involve correctly matching a molecularly targeted therapy to the unique genetic and molecular composition of each individual lymphoma. In this Review, we discuss current and emerging biomarkers that can guide treatment decisions for patients with lymphoma, and explore the potential challenges and strategies for making biomarker-driven personalized medicine a reality in the cure and management of this disease.
现代基因组学和癌症生物学的进步，产生了关于淋巴瘤分子发病机制的前所未有的知识体系。淋巴瘤的不同组织学亚型在分子上具有异质性，很可能起源于不同的致癌机制。随着淋巴瘤生物学的这些进展，已经开发出了几类新的分子靶向药物，它们在不同类型的淋巴瘤中的疗效不同。一般来说，治疗淋巴瘤的新药的开发主要是经验性的，对分子靶点的了解有限，以及药物对靶点的影响。因此，观察到的临床反应的可变性可能是由于潜在的分子异质性。在个性化医学时代，治疗淋巴瘤患者的挑战将涉及将分子靶向治疗正确地与每个个体淋巴瘤的独特基因和分子组成相匹配。在这篇综述中，我们讨论了目前和新兴的生物标志物，这些标志物可以指导淋巴瘤患者的治疗决策，并探讨了在治愈和管理这种疾病方面实现基于生物标志物的个性化医学的潜在挑战和策略。
