Biology Informs Treatment Choices in Diffuse Large B Cell Lymphoma

Matthew J. Butler, Ricardo C.T. Aguiar

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The effective deployment of rationally developed therapies for diffuse large B cell lymphoma (DLBCL) requires rapid assimilation of new biological data. Within this framework, here we address topical issues at the intersection of DLBCL biology and the clinic. We discuss targeting of B cell receptor (BCR) signaling, with emphasis on identifying patients who may benefit from this maneuver and how to best achieve it. We address strategies to modulate the DLBCL microenvironment, including the use of immune checkpoint inhibitors in selected DLBCL subsets, and the potential activity of alternative antiangiogenic therapies. Lastly, we highlight the emerging recognition of MYC and BCL2 coexpression as the most robust predictor of DLBCL outcome, and discuss rationally conceived experimental approaches to treat these high-risk patients. DLBCL is an 'umbrella entity' encompassing multiple biologically discrete disorders.The characterization of the molecular and cellular underpinnings of the various subsets of DLBCL has started to influence treatment choices, and is paving the way for the development of tailored therapeutics for specific DLBCL subtypes.The cell of origin classifier is often used to select candidates for targeted inhibition of BCR signaling.Anatomically distinct DLBCL subsets (testicular, central nervous system, and mediastinal) have a genetic makeup that makes them particularly responsive to PD-1/PD-L1 inhibitors.Dual expression of MYC and BCL2, as defined by immunohistochemistry, has emerged as the most powerful prognostic marker in DLBCL, and identifies a subset of patients with an extremely poor response to first-line R-CHOP therapy.

Original languageEnglish (US)
JournalTrends in Cancer
DOIs
StateAccepted/In press - 2017

Keywords

  • Angiogenesis
  • B-cell receptor
  • Immune checkpoint inhibitors
  • Lymphoma
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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