Animal Models of Lung Cancer: Characterization and Use for Chemoprevention Research

Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
Progress in molecular biology and translational science (Impact Factor: 3.49). 01/2012; 105:211-26. DOI: 10.1016/B978-0-12-394596-9.00007-X
Source: PubMed


Of the potential sites of cancer development, cancer of the lung accounts for the highest number of cancer deaths each year in the United States (Jemal et al., 2010(1)). Based on its histopathological features, lung cancer is grouped into small cell lung cancer (SCLC; ∼20%) and non-SCLC (NSCLC; ∼80%), which is further divided into three subtypes: squamous cell carcinoma (∼30%), adenocarcinoma (∼50%), and large cell lung carcinoma. Every subtype of lung cancer has a relatively low 5-year survival rate that is attributed, in part, to the fact that they are routinely diagnosed at later histologic stages. Due to this alarming statistic, it is necessary to develop not only new and effective means of treatment but also of prevention. One of the promising approaches is chemoprevention which is the use of synthetic or natural agents to inhibit the initial development of or further progression of early lung lesions (Hong and Sporn, 1997). Many compounds have been identified as potentially effective chemopreventive agents using animal models. Most chemopreventive studies have been performed using mouse models which were developed to study lung adenomas or adenocarcinomas. More recently, models of squamous cell lung cancer and small cell lung cancer have also been developed. This review seeks to highlight mouse models which we helped to develop and presents the results of recent chemopreventive studies that we have performed in models of lung adenocarcinoma, squamous cell carcinoma, and small cell lung cancer.

10 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Therapeutic vaccines are different from the well-known prophylactic vaccines in that they are designed to treat patients already suffering from a disease instead of preventing the disease in healthy individuals. Several therapeutic vaccines are today in late-stage clinical development for non-small-cell lung cancer. These vaccines use different approaches including peptides, cell lines and viral vectors, and explore different settings within the pathology. Some are given in monotherapy while others are combined with the classic therapies used with non-small-cell lung cancer. This review gives a summary of the therapeutic vaccines currently in late-stage clinical development for non-small-cell lung cancer.
    Expert Review of Vaccines 03/2013; 12(3):263-70. DOI:10.1586/erv.13.14 · 4.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we investigated the chemopreventive activity of Korea white ginseng (KWG) in a mouse lung SCC model. N-nitroso-trischloroethylurea (NTCU) was used to induce lung tumors in female Swiss mice, and KWG was given orally. KWG significantly reduced the percentage of lung SCCs from 26.5% in the control group to 9.1% in the KWG group, meantime, increased percentage of normal bronchial and hyperplasia. KWG was also found to greatly reduce squamous cell lung tumor area from an average of 9.4% in control group to 1.5% in the KWG group. Treatment with KWG decreased Ki-67 staining, suggesting that the lung tumor inhibitory effects of KWG were partly through inhibition of proliferation. HPLC/MS identified 10 ginsenosides from KWG extracts, Rb1 and Rd being most abundant as detected in mouse blood and lung tissue. The tumor inhibitory effects of KWG are mediated by inhibition of AP-1, as demonstrated by in vitro study conducted on AP-1/ NFkB dependent mouse NSCLC cell lines. Western blotting of lung tissues also indicated that NTCU upregulated AP-1 through phosphorylation of JNK,which was down regulated by KWG in concurrence with its chemoprevention function.
    Cancer Prevention Research 04/2013; 6(6). DOI:10.1158/1940-6207.CAPR-12-0366 · 4.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The effectiveness of anticancer therapies relies on the ability of these substances to eliminate selectively the malignant cells with little or no toxicity to normal cells. The isolation in most human tumors of a rare subpopulation of cancer stem cells (CSCs) associated with chemo resistance lead to the "stem cell theory" (SCT). The SCT proposed that eliminating this fraction will eventually cure cancer, but experimental data supporting this classical view are controversial and are now being gradually replaced by other models. These novel models of cancer biology predict that to cure cancer only drugs or combination of drugs that eliminate all (CSCs and non-CSCs) cancer cells at once ("pankiller drugs") will be effective. The search for pankillers drugs will require tests to assess (i) the elimination of all cancer cells in in vitro systems and (ii) the ability to eradicate the tumors and prevent tumor relapse in in vivo systems. However, at present, most drugs are being tested in assays that can only provide a picture of the short-term activity of anticancer compounds. This in part explains why only a small fraction of the drugs that enter clinical trials are actually approved for clinical use. This article will provide a concise review of the systems, assays, and endpoint parameters routinely used to screen for potential anticancer drugs, and proposes, based in the current knowledge of cancer biology, a more rationale anticancer drug-screening program.
    Current Medicinal Chemistry 05/2013; 21(35). DOI:10.2174/09298673113209990009 · 3.85 Impact Factor
Show more