Convergent Evolution, Evolving Evolvability, and the Origins of Lethal Cancer
Open Access
- 31 March 2020
- journal article
- review article
- Published by American Association for Cancer Research (AACR) in Molecular Cancer Research
- Vol. 18 (6), 801-810
- https://doi.org/10.1158/1541-7786.mcr-19-1158
Abstract
Advances in curative treatment to remove the primary tumor have increased survival of localized cancers for most solid tumor types, yet cancers that have spread are typically incurable and account for >90% of cancer-related deaths. Metastatic disease remains incurable because, somehow, tumors evolve resistance to all known compounds, including therapies. In all of these incurable patients, de novo lethal cancer evolves capacities for both metastasis and resistance. Therefore, cancers in different patients appear to follow the same eco-evolutionary path that independently manifests in affected patients. This convergent outcome, that always includes the ability to metastasize and exhibit resistance, demands an explanation beyond the slow and steady accrual of stochastic mutations. The common denominator may be that cancer starts as a speciation event when a unicellular protist breaks away from its multicellular host and initiates a cancer clade within the patient. As the cancer cells speciate and diversify further, some evolve the capacity to evolve: evolvability. Evolvability becomes a heritable trait that influences the available variation of other phenotypes that can then be acted upon by natural selection. Evolving evolvability may be an adaptation for cancer cells. By generating and maintaining considerable heritable variation, the cancer clade can, with high certainty, serendipitously produce cells resistant to therapy and cells capable of metastasizing. Understanding that cancer cells can swiftly evolve responses to novel and varied stressors create opportunities for adaptive therapy, double-bind therapies, and extinction therapies; all involving strategic decision making that steers and anticipates the convergent coevolutionary responses of the cancers.Keywords
Funding Information
- Swedish Research Council (2015-04693)
- Crafoord Foundation
- The Swedish Royal Physiograpic Society of Lund
- European Union's Horizon
- NIH (R01CA170595, NCI U54CA143970-05)
- Prostate Cancer Foundation (U54CA143803, CA163124, CA093900, CA143055)
- Prostate Cancer Foundation
This publication has 100 references indexed in Scilit:
- Exploiting Evolution To Treat Drug Resistance: Combination Therapy and the Double BindMolecular Pharmaceutics, 2012
- Repeatability and Contingency in the Evolution of a Key Innovation in Phage LambdaScience, 2012
- Clonal evolution in cancerNature, 2012
- Tumor heterogeneity: Causes and consequencesBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2009
- Cell Fusion as a Hidden Force in Tumor ProgressionCancer Research, 2009
- Lager yeasts possess dynamic genomes that undergo rearrangements and gene amplification in response to stressCurrent Genetics, 2008
- Loss of Self‐Incompatibility and Its Evolutionary ConsequencesInternational Journal of Plant Sciences, 2008
- Mutation as a Stress Response and the Regulation of EvolvabilityCritical Reviews in Biochemistry and Molecular Biology, 2007
- Multidrug resistance in cancer: role of ATP–dependent transportersNature Reviews Cancer, 2002
- THE DISTRIBUTION OF SECONDARY GROWTHS IN CANCER OF THE BREAST.The Lancet, 1889