Mechanisms of cancer resistance in long-lived mammals

  title={Mechanisms of cancer resistance in long-lived mammals},
  author={Andrei Seluanov and Vadim N. Gladyshev and Jan Vijg and Vera Gorbunova},
  journal={Nature Reviews Cancer},
Cancer researchers have traditionally used the mouse and the rat as staple model organisms. These animals are very short-lived, reproduce rapidly and are highly prone to cancer. They have been very useful for modelling some human cancer types and testing experimental treatments; however, these cancer-prone species offer little for understanding the mechanisms of cancer resistance. Recent technological advances have expanded bestiary research to non-standard model organisms that possess unique… 
Comparative analysis of long noncoding RNAs in long-lived mammals provides insights into natural cancer-resistance
The genome widely identified long noncoding RNA (lncRNA) transcripts of two longevous mammals and featured their sequence traits, expression patterns, and their correlations with cancer-resistance provided the basis for lncRNA researches in perspectives of evolution and anti-cancer studies.
Age‐dependent expression of cancer‐related genes in a long‐lived seabird
It is suggested here that seabirds are promising, albeit currently completely ignored candidates for studying cancer defense mechanisms, as they have a longer maximum life span than expected from their body size and rates of energy metabolism and may have thus evolved mechanisms to limit neoplasia progression, especially at older ages.
Insights on cancer resistance in vertebrates: reptiles as a parallel system to mammals
It is highlighted how longlived and largebodied organisms are a natural resource for investigating the molecular mechanisms that underlie nontransmissible cancer resistance and increased tumour suppression in mammals.
Naked Mole-Rats: Resistant to Developing Cancer or Good at Avoiding It?
The naked mole-rat (NMR, Heterocephalus glaber), an exceptionally long-lived rodent, displays significant cancer resistance with only a small number of animals being reported to exhibit spontaneous neoplasms.
Beyond tradition and convention: benefits of non-traditional model organisms in cancer research.
It is proposed that assimilating information from a variety of long-lived, large, genetically diverse, and immunocompetent species that live in natural environments and do develop cancer spontaneously (or do not develop cancer at all) will lead to a more comprehensive understanding of human cancers.
Increased risk of cancer in dogs and humans: A consequence of recent extension of lifespan beyond evolutionarily determined limitations?
The cancer‐protective mechanisms that restrain risk at comparable levels to other species for their adapted lifespan are incapable of providing cancer protection over this recent, drastic, and widespread increase in longevity.
The genome of North American beaver provides insights into the mechanisms of its longevity and cancer resistance
A significantly improved beaver genome assembly is utilized to assess evolutionary changes in gene coding sequences, copy number, and expression, and several genes involved in DNA repair showed a higher expression in beavers which is consistent with the trend observed in other long-lived mammals.
The Evolution of Human Cancer Gene Duplications across Mammals
The strongest association between longevity and copy numbers of genes that are both germline and somatic tumor suppressor genes are found, suggesting selection has acted to suppress both hereditary and sporadic cancers.
Revelations About Aging and Disease from Unconventional Vertebrate Model Organisms.
It is proposed that exploring a wider range of unconventional vertebrates will provide important resources to study antiaging mechanisms that are potentially applicable to humans.


Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans.
Elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53, and could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression.
Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism
Cancer resistance of blind mole rats Spalax is suggested to be conferred by massive necrotic response to overproliferation mediated by p53 and Rb pathways, and triggered by the release of IFN-β.
Regulation of Nrf2 signaling and longevity in naturally long-lived rodents
Surprisingly, species longevity was not linked to the protein levels of Nrf2 itself, but rather showed a significant (P < 0.01) negative relationship with the regulators Kelch-like ECH-Associated Protein 1 (Keap1) and β-transducin repeat-containing protein (βTrCP), which target NRF2 for degradation.
Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat
It is proposed that the additional layer of protection conferred by two-tiered contact inhibition contributes to the remarkable tumor resistance of the naked mole-rat.
Resistance to experimental tumorigenesis in cells of a long‐lived mammal, the naked mole‐rat (Heterocephalus glaber)
Rapid crisis is a response of oncogene‐expressing NMR cells to growth in an in vivo environment, which requires anchorage independence, and hTERT permits cells to avoid crisis and to achieve malignant tumor growth.
Lineage selection and the evolution of multistage carcinogenesis
  • L. Nunney
  • Biology
    Proceedings of the Royal Society of London. Series B: Biological Sciences
  • 1999
The ‘two–hit’ model so successfully applied to retinoblastoma is unlikely to be generally applicable to other human cancers; instead, more complex scenarios are expected to dominate, with complexity depending upon a tissue's size and its pattern of proliferation.
Evolution of telomere maintenance and tumour suppressor mechanisms across mammals
The model of the evolution of tumour suppressor mechanisms and telomeres is refined and it is proposed that two different strategies evolved in small and large species because small-bodied species cannot tolerate small tumours that form prior to activation of the telomere barrier, and must instead use telomer-independent strategies that act earlier, at the hyperplasia stage.
Distinct tumor suppressor mechanisms evolve in rodent species that differ in size and lifespan
It is suggested that repression of telomerase activity mitigates the increased risk of cancer in larger‐bodied species but not necessarily longer‐lived ones, which implies that other tumor suppressor mechanisms must mitigate increased cancer risk in long‐lived species.
INK4 locus of the tumor-resistant rodent, the naked mole rat, expresses a functional p15/p16 hybrid isoform
This work shows that the naked mole rat INK4 locus encodes an additional product, a hybrid between p15INK4b and p16INK4a, which may contribute to tumor resistance and longevity of the Naked mole rat and hypothesizes that the presence of the fourth product, pALTink4a/b of the INK8/b locus in the naked Mole rat, contributes to the increased resistance to tumorigenesis of this species.