title: Preclinical models of multiple myeloma: a critical appraisal.
abstract: BACKGROUND
  Preclinical models, by definition, are an approximation of reality, and their use in developing anticancer drugs is eagerly explored. Positive clinical correlations have been identified with different test systems, in addition to limitations and a need to improve preclinical model systems. Predicting whether a potential new anticancer agent will have a positive therapeutic index in patients remains a challenge.
  
  
  METHODS
  We here review the fundamental requirements and remarkable progress of preclinical in vitro and in vivo assays used to assess the therapeutic potential of experimental anticancer drugs in multiple myeloma (MM). In MM, the interaction with the bone marrow microenvironment (BMM) plays a crucial role in disease progression, including resistance to antimyeloma agents. In vitro and in vivo approaches are, therefore, discussed with respect to their ability to mimic the important characteristics of MM and its BMM. In general, MM models should parallel the biological, genetic, etiological, immunological and therapeutic properties of the human disease.
  
  
  CONCLUSIONS
  All models discussed here have their defined strengths, but also limitations with respect to their predictive features. Understanding the preclinical models in a more profound way should lead to optimized clinical trials, thereby expanding the therapeutic arsenal and improving patient outcome further.
authors.affiliation: Freiburg University Medical Center (UKF), Department head in vivo tumorbiology, Oncotest GmbH, Freiburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Schüler
authors.forename: Daniel
authors.initials: D
authors.lastname: Ewerth
authors.forename: Johannes
authors.initials: J
authors.lastname: Waldschmidt
authors.forename: Ralph
authors.initials: R
authors.lastname: Wäsch
authors.forename: Monika
authors.initials: M
authors.lastname: Engelhardt
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents