Cancer in rodents: does it tell us about cancer in humans?

Key Points

  • Whereas laboratory rodents (namely mice and rats) are similar to humans in some aspects, there are important differences among mammalian species that make valid interpretation and extrapolation of the results from rodent cancer experiments to humans problematic.

  • The five most common human cancers are those of the breast (female), the prostate (male), and the lungs, colon, and stomach (both sexes). Mammary tumours are also common in rodents. However, there are no rat or mouse strains that exhibit a high incidence of spontaneous carcinomas of the stomach or colon.

  • A decrease in the overall risk of cancer owing to old age has been recorded in both human and rodent studies. Three important factors could be responsible for this intriguing decline: detection bias, differential selection, and the effects of individual ageing. Studies in rodents argue against a diagnostic bias as a leading cause.

  • The risk of cancer has increased over time in most human populations. Why this is remains unclear, but addressing this problem is crucial for understanding the nature of cancer.

  • Some studies indicate that the differences in cancer incidence rates between males and females are similar in rodents and humans. This is a surprising finding that requires additional explanation.

  • Whereas tumours often grow at a slower rate during old age, the chances for survival of a transplanted tumour in a recipient host often increases with rodent age. This is in agreement with human data indicating that ageing can both decelerate tumour growth and increase the chances of latent tumour survival in older organisms.

  • The spontaneous regression of tumours is a rare phenomenon in adult humans, whereas it is common in mature laboratory rodents. This effect and its implications need further investigation.

  • Few rodent carcinogens were established as clearly carcinogenic to humans. Similarly, some human carcinogens are not carcinogenic to rodents. This creates a significant problem for interpreting the results of animal experiments with carcinogens in relation to humans.

  • These and other differences warn against the simple extrapolation of the results of rodent experiments to humans and call for further investigation of this important problem to reliably predict cancer risks, as well as foster success in treating human cancers based on data from laboratory animal studies.

Abstract

Information obtained from animal models (mostly mice and rats) has contributed substantially to the development of treatments for human cancers. However, important interspecies differences have to be taken into account when considering the mechanisms of cancer development and extrapolating the results from mice to humans. Comparative studies of cancer in humans and animal models mostly focus on genetic factors. This review discusses the bio-epidemiological aspects of cancer manifestation in humans and rodents that have been underrepresented in the literature.

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Figure 1: Typical age-patterns of overall cancer incidence and mortality rates in humans in the USA.
Figure 2: Age-patterns of cancer incidence rate in laboratory rodents of different strains.
Figure 3: Time trends in overall cancer incidence rate.
Figure 4: Patterns of sex difference in cancer incidence.

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Acknowledgements

The authors wish to thank James W. Vaupel for the opportunity to conduct substantial parts of this work at the Max Planck Institute for Demographic Research, Germany. We are thankful to Mark A. Zabezhinski and Igor Akushevich for their comments on the paper. We are also thankful to Virginia Lewis for help in preparing this manuscript. This research was partly supported by NIH/NIA grants and by a grant from the President of the Russian Federation.

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Correspondence to Vladimir N. Anisimov or Svetlana V. Ukraintseva.

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DATABASES

Entrez Gene

Trp53

National Cancer Institute

bladder tumours

colon cancer

endometrial carcinomas

leukaemia

lymphomas

skin carcinoma

stomach cancer

Glossary

CANCER INCIDENCE RATE

A proportion of new cancer cases (registered for the first time) in a population of a given age.

PREVALENCE OF CANCER

A proportion of individuals with a diagnosed cancer (no matter when the diagnosis was made) in a population of a given age. The prevalence characterizes the cancer burden.

CANCER MORTALITY RATE

A proportion of cancer deaths in a population of a given age.

POLYCYCLIC AROMATIC HYDROCARBONS

Their metabolites (diol epoxides) bind DNA and induce point-mutations in oncogenes (for example, HRAS).

NITROSO COMPOUNDS

Potent alkylating mutagens and carcinogens. The most important target in DNA is guanine at the O6 position.

2-NAPHTHYLAMINE

The oxidation of 2-naphthylamine at the amine group leads to the formation of hydroxylamine, which binds DNA in the target tissue.

ONTOGENY

The total of the stages of an organism's life history.

HYPERINSULINAEMIA

An increased level of insulin in the serum.

ANTIDIABETIC MEDICINES

Antidiabetic drugs, phenformin (1-phenylethylbiguanide), buformin (1-butylbiguanide hydrochloride) and metformin (N,N-dimethylbiguanide) decrease the blood glucose level and increase the susceptibility of tissues to insulin.

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Anisimov, V., Ukraintseva, S. & Yashin, A. Cancer in rodents: does it tell us about cancer in humans?. Nat Rev Cancer 5, 807–819 (2005). https://doi.org/10.1038/nrc1715

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