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

Pienta, Kenneth J ; Hammarlund, Emma U LU ; Axelrod, Robert ; Amend, Sarah R and Brown, Joel S (2020) In Molecular cancer research : MCR
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... (More)

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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organization
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Contribution to journal
publication status
epub
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in
Molecular cancer research : MCR
publisher
American Association for Cancer Research
external identifiers
  • scopus:85085903949
  • pmid:32234827
ISSN
1557-3125
DOI
10.1158/1541-7786.MCR-19-1158
language
English
LU publication?
yes
additional info
©2020 American Association for Cancer Research.
id
f8dc6977-2e18-4b82-9cc1-3c1bbc34f9e1
date added to LUP
2020-05-18 08:55:37
date last changed
2020-10-20 04:55:58
@article{f8dc6977-2e18-4b82-9cc1-3c1bbc34f9e1,
  abstract     = {<p>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 &gt;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.</p>},
  author       = {Pienta, Kenneth J and Hammarlund, Emma U and Axelrod, Robert and Amend, Sarah R and Brown, Joel S},
  issn         = {1557-3125},
  language     = {eng},
  month        = {05},
  publisher    = {American Association for Cancer Research},
  series       = {Molecular cancer research : MCR},
  title        = {Convergent Evolution, Evolving Evolvability, and the Origins of Lethal Cancer},
  url          = {http://dx.doi.org/10.1158/1541-7786.MCR-19-1158},
  doi          = {10.1158/1541-7786.MCR-19-1158},
  year         = {2020},
}