Mouse Models of Lung Cancer

Lung cancer has increased in incidence throughout the 20th
century and is now the most common cancer in the Western
World. Compared to other cancers, the pathogenesis of lung
cancer remains highly elusive because of its aggressive biologic
nature and considerable heterogeneity. Most patients die
of progressive metastatic diseases despite aggressive local and
systemic therapies. To better understand the different steps in
lung cancer progression and, most importantly, to devise more
effective lung cancer therapies, there is considerable need for
improved experimental models of lung cancer.
Currently, several animal species are widely used for experimental
lung cancer research, including dogs, primates, hamsters,
and mice. 1–3 Among the different animal species, mice have
become the preferred model to study lung cancer development
and progression because of their relative cost-effectiveness, the
ease of genetic manipulation, and the large number of genetically
altered mice available for experimentation. Primary lung
tumors in mice have morphologic, histogenic, and molecular
features similar to human lung adenocarcinoma, particularly
the bronchioloalveolar carcinoma subtype. Because of this, and
because of the genetic homology between man and mouse, this
model system is receiving intense research attention.
Three major different models are commonly used to induce
lung cancer in mice, namely chemically and/or carcinogen-
induced lung cancer, orthotopic models of lung cancer,
and genetic models of lung cancer. In addition, spontaneous
lung cancer develops in approximately 3% of mice and has
a strain-dependent incidence in inbred mice (Fig. 13.1). 4
Mice that develop spontaneous lung tumors also respond to
chemicals and carcinogens, thus making them an ideal system
to study chemically and/or carcinogen-induced lung cancer.
Each of the mouse models available allows the analysis of different
aspects of the disease, such as carcinogenesis, initiation,
promotion, metastasis, as well as host–tumor interaction and
angiogenesis. For example, the chemically induced lung cancer
models allow the study of tumor initiation and promotion;
the orthotopic model allows the analysis of primary as well as
metastatic lung cancers, whereas the genetic model allows the
13
Mouse Models of Lung Cancer
C H A P T E R
Ambra Pozzi
identification of genes involved in lung cancer development
and progression.
Despite the fact that these models reflect the histopathology
and the steps involved in lung cancer progression, each of them
has limitations. These include lack of metastasis (genetic- and
chemically induced lung cancer), the development of tumors
only late in their course of development (chemically induced
lung cancer), and the development of only one subset of lung
cancer, namely adenoma and/or adenocarcinoma. For these reasons,
more than one model is used when studying the etiology,
pathogenesis, and progression of lung cancer.
In this chapter, we will describe the main features of the
available mouse models of lung cancer, and how these models can
be used for translational research. We will mainly point out practical
benefits, such as their application for identifying therapeutic
strategies for the treatment and prevention of lung cancer.