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

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

Pienta, Kenneth J (författare): Johns Hopkins University School of Medicine

Hammarlund, Emma U (författare): Lund 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

Axelrod, Robert (författare): University of Michigan

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Amend, Sarah R (författare): Johns Hopkins University School of Medicine

Brown, Joel S (författare): H. Lee Moffitt Cancer Center & Research Institute

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(creator_code:org_t)

2020
2020
Engelska 10 s.
Ingår i: Molecular cancer research : MCR. - 1557-3125. ; 18:6, s. 801-810

Relaterad länk:: http://dx.doi.org/10...; visa fler...; https://lup.lub.lu.s...; https://doi.org/10.1...; visa färre...

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Abstract Ämnesord

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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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
NATURVETENSKAP -- Biologi -- Evolutionsbiologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Evolutionary Biology (hsv//eng)

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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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