Biology Informs Treatment Choices in Diffuse Large B Cell Lymphoma

Trends Cancer. 2017 Dec;3(12):871-882. doi: 10.1016/j.trecan.2017.09.008. Epub 2017 Nov 6.

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.

Keywords: B-cell receptor; angiogenesis; immune checkpoint inhibitors; lymphoma; targeted therapy.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • Prednisone / adverse effects
  • Prednisone / therapeutic use
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-myc / antagonists & inhibitors
  • Proto-Oncogene Proteins c-myc / genetics*
  • Receptors, Antigen, B-Cell / antagonists & inhibitors
  • Receptors, Antigen, B-Cell / genetics
  • Rituximab
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics
  • Vincristine / adverse effects
  • Vincristine / therapeutic use

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • BCL2 protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • R-CHOP protocol
  • Receptors, Antigen, B-Cell
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone