Available online 11 March 2024, 108631

Mouse models of disease play a pivotal role at all stages of cancer drug development. Cell-line derived subcutaneous tumour models are predominant in early drug discovery, but there is growing recognition of the importance of the more complex orthotopic and metastatic tumour models for understanding both target biology in the correct tissue context, and the impact of the tumour microenvironment and the immune system in responses to treatment. The aim of this review is to highlight the value that orthotopic and metastatic models bring to the study of tumour biology and drug development while pointing out those models that are most likely to be encountered in the literature. Important developments in orthotopic models, such as the increasing use of early passage patient material (PDXs, organoids) and humanised mouse models are discussed, as these approaches have the potential to increase the predictive value of preclinical studies, and ultimately improve the success rate of anticancer drugs in clinical trials.

Preclinical

Drugs

Orthotopic

Metastatic

Xenograft

Syngeneic

PDX

Organoids

American type culture collection

bioluminescence imaging

cell line-derived xenograft

circulating tumour cells

European collection of authenticated cell cultures

ethylenediaminetetraacetic acid

fibroblast activation protein inhibitor

human leukocyte antigen

hematopoietic stem cell

major histocompatibility complex

magnetic resonance imaging

peripheral blood mononuclear cells

patient-derived orthotopic xenograft

patient derived xenograft

positron emission tomography

prostate specific membrane antigen

Institute of Physical and Chemical Research

single photon emission computed tomography

© 2024 The Authors. Published by Elsevier Inc.