title: Preclinical modeling of novel therapeutics in chronic lymphocytic leukemia: the tools of the trade.
abstract: In the last decade our understanding of chronic lymphocytic leukemia (CLL) biology and pathogenesis has increased substantially. These insights have led to the development of several new agents with novel mechanisms of action prompting a change in therapeutic approaches from chemotherapy-based treatments to targeted therapies. Multiple preclinical models for drug development in CLL are available; however, with the advent of these targeted agents, it is becoming clear that not all models and surrogate readouts of efficacy are appropriate for all drugs. In this review we discuss in vitro and in vivo preclinical models, with a particular focus on the benefits and possible pitfalls of different model systems in the evaluation of novel therapeutics for the treatment of CLL.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. Electronic address: hermanse@mail.nih.gov.
authors.forename: Sarah E M
authors.initials: SE
authors.lastname: Herman
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Adrian
authors.initials: A
authors.lastname: Wiestner
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D051379:Mice; D059016:Tumor Microenvironment; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents
keywords: Chronic lymphocytic leukemia; Co-culture systems; Mouse models