The use of non-traditional models in the study of cancer resistance—the case of the naked mole rat

Alyssa Shepard, Joseph L. Kissil, PhD
The use of non-traditional models in the study of cancer resistance—the case of the naked mole rat

We all love a good underdog story, and the journey of naked mole rats from a suspected diseased mole rat species to model organism for cancer prevention research can certainly be considered one. While they were first described in 1845 by Eduard Rüppell, the relevance of the naked mole rats to cancer research would not become apparent for more than a century, when the first captive colonies were established for behavioral studies. These initial studies, conducted over a few decades, led to the observation of a prolonged lifespan, much longer than expected based on their size. In turn, this observation led to the next epiphany that, despite this long lifespan, naked mole rats did not appear to present with tumors. In fact, it was hypothesized that they would never develop cancer, until the first observations were published in 2016.

While the full journey from rags to riches is not catalogued in this review, the trajectory of naked mole rat studies is what led to the discovery of their remarkable cancer resistance and is referenced in our first figure. Our lab has been studying naked mole rats in the context of cancer prevention for the past few years. This review, probably like many recent reviews, is a consequence of lab work being halted for a few weeks due to COVID-19 related coronavirus. It has offered us the opportunity to step back, evaluate the field, and gain a deeper understanding of where we should be heading, in terms of our own research projects on cancer in the naked mole rat.

This analysis has illustrated that the two biggest factors at the core of the naked mole rat’s unusual biology are likely to be enhanced genome and protein stability. In this review, we parse these two factors into smaller bites, but they are likely the driving forces behind their remarkable longevity and resistance to cancer. Genome stability is a result of mechanisms such as enhanced regulation of the cell cycle and altered DNA repair, while the protein stability stems from resistance to oxidative damage and apparent increased sensitivity to any dysfunction of their protective mechanisms.

The papers discussed in this review have led to a solid rationale for the use of the naked mole rat as a model for understanding cancer resistance and applying this information to cancer prevention.  Like any good scientific exploration, they leave many questions unanswered, and often generate new questions that are promising future research directions. It’s exciting to be a part of a research field where so much is unknown, and the loose threads presented in these papers suggest that we will see a rapid expansion of knowledge in this area in the coming years. The hope is that we can eventually utilize what Mother Nature has perfected over thousands of years of evolution to the benefit of humanity, and that the unusual biology of the naked mole rat will provide some of the answers we have been looking for in cancer prevention research.

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