title: Can oncology recapitulate paleontology? Lessons from species extinctions.
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.
authors: Evolution and Cancer Laboratory, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors: Viola
authors: V
authors: Walther
authors: Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors: Crispin T
authors: CT
authors: Hiley
authors: Department of Pathology, USC Keck School of Medicine, Hoffman Medical Research Center 211, 2011 Zonal Avenue, Los Angeles, CA 90089-9092, USA.
authors: Darryl
authors: D
authors: Shibata
authors: Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors: Charles
authors: C
authors: Swanton
authors: Department of Ecology and Evolutionary Biology, Yale University, 165 Prospect Street, New Haven, CT 06511, USA.
authors: Paul E
authors: PE
authors: Turner
authors: Center for Evolution and Cancer, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 2340 Sutter Street, San Francisco, CA 94143, USA.
authors: Carlo C
authors: CC
authors: Maley
mesh_terms: D053476:Extinction, Biological; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010163:Paleontology / Q000379:methods*; D011379:Prognosis; D057170:Translational Research, Biomedical / Q000379:methods; D059016:Tumor Microenvironment