Convergent Evolution, Evolving Evolvability, and the Origins of Lethal Cancer

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Pienta, Kenneth JJohns Hopkins University School of Medicine (författare)

Convergent Evolution, Evolving Evolvability, and the Origins of Lethal Cancer

Artikel/kapitelEngelska2020

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2020
10 s.

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LIBRIS-ID:oai:lup.lub.lu.se:f8dc6977-2e18-4b82-9cc1-3c1bbc34f9e1
https://lup.lub.lu.se/record/f8dc6977-2e18-4b82-9cc1-3c1bbc34f9e1URI
https://doi.org/10.1158/1541-7786.MCR-19-1158DOI

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Språk:engelska
Sammanfattning på:engelska

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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.

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Hammarlund, Emma ULund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments,University of Southern Denmark(Swepub:lu)med-ehd (författare)
Axelrod, RobertUniversity of Michigan (författare)
Amend, Sarah RJohns Hopkins University School of Medicine (författare)
Brown, Joel SH. Lee Moffitt Cancer Center & Research Institute (författare)
Johns Hopkins University School of MedicineAvdelningen för translationell cancerforskning (creator_code:org_t)

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Ingår i:Molecular cancer research : MCR18:6, s. 801-8101557-3125

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Av författaren/redakt...: Pienta, Kenneth ...; Hammarlund, Emma ...; Axelrod, Robert; Amend, Sarah R; Brown, Joel S

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Cell och molekyl ...

NATURVETENSKAP: NATURVETENSKAP; och Biologi; och Evolutionsbiolog ...

Artiklar i publikationen: Molecular cancer ...

Av lärosätet: Lunds universitet

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