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Can oncology recapitulate paleontology? Lessons from species extinctions

Key Points

  • The problem of curing cancer is equivalent to the extinction of a genetically diverse, single-celled organismal species

  • Most extinctions are thought to occur through a 'press-pulse' dynamic in which multiple stressors reduce population size and habitat, and then an abrupt perturbation finally causes population collapse

  • Cancer therapy can be improved by mimicking causes of species extinction, including reducing neoplastic evolvability, destroying habitat, targeting escape phenotypes, and maintaining multiple, diverse selective pressures for many cell generations

  • The characteristics that make a species resistant to extinction should also be useful prognostic markers for a neoplasm's resistance to therapy

  • Targeting a tumour's habitat and evolvability remain promising, but relatively unexplored, avenues for future research

Abstract

Although we can treat cancers with cytotoxic chemotherapies, target them with molecules that inhibit oncogenic drivers, and induce substantial cell death with radiation, local and metastatic tumours recur, resulting in extensive morbidity and mortality. Indeed, driving a tumour to extinction is difficult. Geographically dispersed species of organisms are perhaps equally resistant to extinction, but >99.9% of species that have ever existed on this planet have become extinct. By contrast, we are nowhere near that level of success in cancer therapy. The phenomena are broadly analogous—in both cases, a genetically diverse population mutates and evolves through natural selection. The goal of cancer therapy is to cause cancer cell population extinction, or at least to limit any further increase in population size, to prevent the tumour burden from overwhelming the patient. However, despite available treatments, complete responses are rare, and partial responses are limited in duration. Many patients eventually relapse with tumours that evolve from cells that survive therapy. Similarly, species are remarkably resilient to environmental change. Paleontology can show us the conditions that lead to extinction and the characteristics of species that make them resistant to extinction. These lessons could be translated to improve cancer therapy and prognosis.

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Figure 1: Causes of species extinction.
Figure 2: Potential cancer therapies inspired by mechanisms of extinction.

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Acknowledgements

The work of C.T.H. is supported by a National Institute for Health Research Academic Clinical Fellowship. C.S. receives funding from Cancer Research UK, the Rosetrees Trust, the Breast Cancer Research Foundation, the Prostate Cancer Foundation, European Union Framework program 7 grants PREDICT and RESPONSIFY, and the European Research Council. The work of P.E.T. is supported in part by grants from the National Science Foundation (DEB-1021243) and NIH (R01-AI091646). The work of C.C.M. is supported in part by Research Scholar Grant #117209-RSG-09-163-01-CNE from the American Cancer Society, NIH grants P01 CA91955, R01 CA149566, R01 CA170595 and R01 CA140657, and CDMRP Breast Cancer Research Program Award BC132057.

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V.W. researched the data for the article. All authors contributed substantially to discussion of content. V.W., C.T.H., P.E.T. and C.C.M. wrote the article. All authors reviewed and edited the manuscript before submission.

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Correspondence to Carlo C. Maley.

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Walther, V., Hiley, C., Shibata, D. et al. Can oncology recapitulate paleontology? Lessons from species extinctions. Nat Rev Clin Oncol 12, 273–285 (2015). https://doi.org/10.1038/nrclinonc.2015.12

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