Table 3.

Advantages and disadvantages of animal models of bladder cancer

Type	Mechanism	Advantages	Disadvantages	Remarks
Chemically induced mice model	Induced by carcinogens: BBN, FANFT, and MNU	Provides information about the risk of chemical exposure	Low-grade tumors and low rates of metastasis Tumor induction depends on carcinogen and dosage	Studies to validate the effects of the environmental agents and for evaluation of molecular mechanisms during carcinogenesis
Genetically engineered mice model	Induced by cloning oncogenes and/or deleting tumor-suppressing genes	Provides information on the role of specific genes such as oncogenes and tumor suppressors	Homogeneous population of cancer cells	Studies to evaluate the effects of specific genes for bladder tumorigenesis Studies to test novel therapeutic, imaging, or preventive agents
Xenogeneic mice model	Induced by implanting bladder cancer cells, eg, human into immune-deficient mouse	Tumors are of nonrodent origin eg, human	Immune response cannot be assessed Homogeneous population of cancer cells	Studies to test novel therapeutic, imaging, or preventive agents
Syngeneic mice model	Induced by implanting rodent bladder cancer cells into immune-deficient mouse	Tumor microenvironment is same as the tumor is of rodent origin Tumors induced are of rodent origin	Homogeneous population of cancer cells	To test novel therapeutic, imaging, or preventive agents
Orthotopic mice model	Induced by implanting the bladder cancer cells into bladder	Mimic human bladder cancer behavior as microenvironment is closer to natural conditions	High morbidity of mice connected with the surgery of the bladder cancer cells implantation Homogeneous population of cancer cells	To test novel therapeutic, imaging, or preventive agents
Heterotopic mice model	Induced by implanting the bladder cancer cells at the different sites/organs such as bladder, usually subcutaneous	Technically simple model Tumor can be noninvasively detected	Inoculation site/organ is different, thereby the tumor microenvironment is altered Homogeneous population of cancer cells	To test novel therapeutic, imaging, or preventive agents
Companion animals with bladder cancer	Spontaneously occurring bladder cancer in dogs and cats	Naturally occurring heterogeneous population of cancer cells More similar biological and histological appearance to human cancer response to cytotoxic agents Shorter overall life span and more rapid disease progression	More costly than rodent model	To test novel therapeutic, imaging, or preventive agents for papillary and muscle-invasive bladder cancer Epidemiological studies

Abbreviations: BBN, N-butyl-N-(4-hydroxybutyl) nitrosamine; FANFT, N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide; MNU, N-methyl-N-nitrosourea.