Patient-derived tumor xenografts of lymphoproliferative disorders: are they surrogates for the human disease?

Curr Opin Hematol. 2017 Jul;24(4):384-392. doi: 10.1097/MOH.0000000000000349.

Abstract

Purpose of review: Patient-derived tumor xenografts (PDTXs) have emerged as powerful platforms in medical oncology. A plethora of PDTXs were generated to study solid cancers, but limited data are as yet available on hematological diseases. The aim of this review is to describe the state of art of lymphoma PDTXs, discussing future directions for the development of integrated/personalized cancer programs.

Recent findings: In the last decades, several PDTXs of lymphoproliferative disorders have been produced. Most studies focused on acute lymphoblastic leukemias, but consistent results have recently been obtained also for indolent and aggressive B-/T-cell lymphomas. These models have contributed to characterize lymphoma biology and therapy, despite technical and scientific issues have partially limited their application (e.g. high costs, relatively low engraftment rates, lack of human-derived tumor microenvironment, clonal selection of engrafted cells, limited characterization of tumor grafts). In the next future, such limitations should be overcome by new technical approaches and dedicated multiinstitutional programs.

Summary: PDTXs represent an unprecedented opportunity to study the biology and clinical management of lymphoproliferative disorders. Many of the current models display limitations, which will be resolved by rigorous approaches and comprehensive libraries, recapitulating the extreme heterogeneity of such neoplasms.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Heterografts*
  • Humans
  • Lymphoma / genetics
  • Lymphoma / immunology
  • Lymphoma / pathology
  • Lymphoma / therapy
  • Lymphoproliferative Disorders / genetics
  • Lymphoproliferative Disorders / immunology
  • Lymphoproliferative Disorders / pathology*
  • Lymphoproliferative Disorders / therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Xenograft Model Antitumor Assays*

Substances

  • Antineoplastic Agents