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Essential Insights | How Many Types of Tumor Animal Models Are There, Exactly?

Introduction

Tumors have become a major threat to public health, with mortality rates second only to those of cardiovascular diseases, and cancer-related deaths remain persistently high. Consequently, tumor research has emerged as a central focus of modern biological science, and tumor animal models play an indispensable role in elucidating tumorigenesis and progression, as well as in drug discovery and development.

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Based on their etiological origins, tumor animal models are classified into: spontaneous tumor models, induced tumor models, tumor cell line–based xenograft models, human‑derived tumor tissue xenograft models, and genetically modified models.

1. Spontaneous tumor animal models

A spontaneous tumor animal model refers to a tumor that develops in experimental animals under natural conditions, without any deliberate human intervention.

Advantages:

① Spontaneous tumors in animals closely resemble the tumorigenesis process in humans, making it easier to extrapolate findings to the human context.

② It can be used to investigate the role of genetic factors in tumorigenesis and the antitumor efficacy of drugs.

Disadvantages:

① Due to substantial inter‑individual variability in tumor growth, it is difficult to obtain a large number of tumor‑bearing animals with uniform tumor growth within a specified time frame.

② The experimental period is relatively long;

③ It also requires a large number of animals and entails substantial costs, thus it is seldom used for routine screening of antitumor drugs.

For example, the MMTV‑PyMT spontaneous mammary carcinoma model: a genetically engineered animal model of spontaneous breast cancer that closely mimics human breast carcinogenesis and exhibits excellent reproducibility, objectivity, and widespread acceptance, making it a classic model for breast cancer research.

2. Experimental tumor animal models

Under experimental conditions, tumors are induced in animals by exposing them to physical, chemical, and biological carcinogens. The most common chemical carcinogens include benzo[a]pyrene, methylcholanthrene, benzidine, nitrosamines, and aflatoxins, among others.

Advantages:

① The model’s inducing factors and conditions can be artificially controlled, resulting in an induction rate far exceeding the natural incidence rate.

②This method is frequently employed to evaluate the effects of suspected carcinogenic factors and to conduct research on tumor etiology and cancer prevention.

Disadvantages:

① Long induction period (3–5 months, or even 1–2 years);

② The tumor formation rate is low, and the animal mortality rate is high.

③ The timing of tumor onset, the anatomical location, and the number of lesions all exhibit phenotypic heterogeneity among individuals.

For example, our laboratory has established an inducible model of colitis and colorectal cancer by adding dextran sulfate sodium (DSS) to the drinking water of mice.

3. Tumor cell-line-derived xenograft model (CDTX model)

Tumor cell lines are transplanted into syngeneic or allogeneic animals to establish tumors. Tumor‑cell‑line xenograft models are the most widely used in vivo approaches for screening anti‑tumor agents; for example, the efficacy of a test compound can be assessed by monitoring specific biomarkers that indicate inhibition of tumor growth. The model most frequently employed in our laboratory for evaluating the antitumor activity of candidate drugs is this type of xenograft.

Advantages:

① Tumor cell line–derived xenografts retain most of the biological characteristics of the primary tumor.

② Nearly all types of human tumors can be used to establish transplantable tumor models in immunodeficient animals;

③ Individual animals exhibit minimal variability in tumor formation, with a high tumorigenic rate and a short experimental duration.

Disadvantages:

① The tumor has a short proliferation time, which differs from human tumors;

②Not all cellular subpopulations of human tumors can be found in xenografts.

③ Generally, immunodeficient animals are required, which entails higher costs.

4. Patient-derived tumor xenograft model (PDTX model)

A model was established by directly engrafting fresh patient tumor tissue into immunodeficient mice. Human tumor xenograft models minimize ex vivo manipulation, thereby more accurately reflecting the tumor’s intrinsic biological characteristics [6].

Advantages:

① The primary advantage is that it preserves the tumor’s stromal heterogeneity and histological characteristics, providing an in vivo model for cancer research—capturing features such as tumor cell morphology, stromal enrichment, the lymphatic and vascular systems, and necrotic areas.

②It can more objectively and comprehensively reflect tumor progression and the response to drug therapy.

Disadvantages:

① Tumors that are implanted exhibit relatively infrequent metastasis.

② High costs and long timelines: establishing a personalized tumor xenograft model requires at least two months.

③ The procedure is technically challenging and has a relatively low tumor‑formation rate, making it comparatively complex to perform, particularly when conducting ectopic transplantation in sites such as the renal capsule.

For example, transplanting fresh human tumors into the renal capsule of immunodeficient mice has opened another important avenue for studying tumor mechanisms and conducting preclinical drug trials; the figure below shows a renal capsule model of prostate cancer.

5. Gene-modified tumor model

Genetically modified tumor models are created by using techniques such as transgenesis, gene targeting, and conditional gene targeting to knock out or insert specific genes, thereby inducing tumorigenesis in animals. These models are typically employed to study precancerous lesions and the processes of tumor initiation and progression.

Advantages:

① It provides excellent material for studying the interactions between environmental factors and genetic backgrounds.

② Transgenic models offer significant advantages for studying the mechanisms of tumorigenesis and tumor immune evasion.

Disadvantages:

① The model-building process is relatively lengthy;

② Higher costs, etc.

For example, when the K-ras gene undergoes mutation, it disrupts intracellular signal transduction, leading to uncontrolled cell proliferation and the development of lung cancer.

Different tumor animal models exhibit distinct oncological characteristics. When conducting research, it is essential to select the most appropriate model based on the experimental objectives and specific aims, and to design a corresponding experimental protocol, in order to arrive at sound scientific conclusions and optimal experimental outcomes.

References:

Siegel R, Miller KD, Jemal A, et al. Cancer statistics, 2016.[J]. CA: A Cancer Journal for Clinicians, 2016, 66(1): 7-30.

Chen W, Zheng R, Baade P D, et al. Cancer statistics in China, 2015.[J]. CA: A Cancer Journal for Clinicians, 2016, 66(2): 115-132.

Hallett M A, Teng B, Hasegawa H, et al. Anti-matrixmetalloproteinase-9 DNAzyme decreases tumor growth in the MMTV-PyMT mouse modelof breast cancer[J]. Breast Cancer Research, 2013, 15(1): 1-11.

De Robertis M, Massi E, Poeta M L, et al. The AOM/DSS murine model for the study of colon carcinogenesis: From pathways to diagnosis and therapy studies[J]. Journal of Carcinogenesis, 2011, 10(1): 9-9.

Qin M, Peng S, Liu N, et al. LG308, a novel synthetic compound with antimicrotubule activity in prostate cancer cells, exerts effective antitumor activity[J]. Journal of Pharmacology and Experimental Therapeutics, 2015, 355(3): 473-483.

Siolas D, Hannon G J. Patient-derived tumor xenografts: transforming clinical samples into mouse models[J]. Cancer research, 2013,73(17): 5315-5319.

Wang J, Hu K, Guo J, et al. Suppression of KRas-mutant cancer through the combined inhibition of KRAS with PLK1 and ROCK[J]. Nature Communications,2016: 11363-11363.