REVIEWS Precision therapy for lymphoma—current state and future directions Andrew M. Intlekofer and Anas Younes Abstract | 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. Intlekofer, A. M. & Younes, A. Nat. Rev. Clin. Oncol. advance online publication 19 August 2014; doi:10.1038/nrclinonc.2014.137
Introduction
Lymphoma Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 330, New York, NY 10065, USA (A.M.I., A.Y.). Correspondence to: A.Y. [email protected]
Lymphoma remains a significant cause of morbidity and mortality worldwide, with an estimated 450,000 new cases and 225,000 deaths annually.1 Lymphoma repre‑ sents a heterogeneous disease for which outcomes can vary greatly.2 The indolent B‑cell lymphomas, such as follicular lymphoma, marginal zone lymphoma, and small lymphocytic lymphoma, remain incurable chronic diseases, requiring patients to undergo repeated expo‑ sures to toxic therapies.3 For the aggressive lymphomas, modern treatment regimens result in long-term sur‑ vival rates ranging from >80% for Hodgkin lymphoma to ~60% for diffuse large B‑cell lymphoma (DLBCL) and to
Introduction
Lymphoma Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 330, New York, NY 10065, USA (A.M.I., A.Y.). Correspondence to: A.Y. [email protected]
Lymphoma remains a significant cause of morbidity and mortality worldwide, with an estimated 450,000 new cases and 225,000 deaths annually.1 Lymphoma repre‑ sents a heterogeneous disease for which outcomes can vary greatly.2 The indolent B‑cell lymphomas, such as follicular lymphoma, marginal zone lymphoma, and small lymphocytic lymphoma, remain incurable chronic diseases, requiring patients to undergo repeated expo‑ sures to toxic therapies.3 For the aggressive lymphomas, modern treatment regimens result in long-term sur‑ vival rates ranging from >80% for Hodgkin lymphoma to ~60% for diffuse large B‑cell lymphoma (DLBCL) and to
