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Clonal evolution and therapy resistance in the era of precision cancer medicine : evolutionary trajectories in pediatric cancer

Karlsson, Jenny LU ; Briggs, Mayen ; Vedi, Aditi and Gisselsson, David LU (2025) In Seminars in Cancer Biology 116. p.121-134
Abstract

Pediatric cancers exhibit complex evolutionary dynamics driven by genetic instability, clonal selection, epigenetic reprogramming, and microenvironmental interactions. Tumor evolution is typically characterized by branching phylogenies, where subclones with unique genetic profiles emerge at different locations and time points. Partly as a result of this diversity, advanced cancers often develop resistance to multiple therapies, complicating treatment strategies. This review explores recurrent themes in clonal evolution across childhood cancers as well as evolution-inspired strategies to counter treatment resistance. A model of dynamic decision making is suggested to accommodate emerging methods for monitoring shifts in a cancer's clonal... (More)

Pediatric cancers exhibit complex evolutionary dynamics driven by genetic instability, clonal selection, epigenetic reprogramming, and microenvironmental interactions. Tumor evolution is typically characterized by branching phylogenies, where subclones with unique genetic profiles emerge at different locations and time points. Partly as a result of this diversity, advanced cancers often develop resistance to multiple therapies, complicating treatment strategies. This review explores recurrent themes in clonal evolution across childhood cancers as well as evolution-inspired strategies to counter treatment resistance. A model of dynamic decision making is suggested to accommodate emerging methods for monitoring shifts in a cancer's clonal landscape and the widening repertoire of precision drugs. A larger drug toolbox will allow for more sophisticated evolutionary stratagems to cure or stabilize cancer, using methods such as adaptive therapy, extinction therapy, and reflexive control therapies. However, there are also inherent limits in predicting and controlling cancer evolution- emphasizing the need for early detection, particularly in the setting of predicting relapse, which disproportionately contributes to cancer related mortality in childhood. Understanding the evolutionary trajectories of pediatric cancers can inform more effective, personalized treatment protocols, ultimately enhancing survival rates and quality of life for young patients.

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type
Contribution to journal
publication status
published
subject
keywords
Childhood cancer, Evolution, Evolutionary therapy, Genetic instability, Pediatric cancer, Selection
in
Seminars in Cancer Biology
volume
116
pages
14 pages
publisher
Academic Press
external identifiers
  • pmid:41067671
  • scopus:105018301640
ISSN
1044-579X
DOI
10.1016/j.semcancer.2025.10.001
language
English
LU publication?
yes
id
a0ee0551-661e-4cd7-96c9-ba8209fadc75
date added to LUP
2026-01-08 08:35:01
date last changed
2026-01-08 08:35:38
@article{a0ee0551-661e-4cd7-96c9-ba8209fadc75,
  abstract     = {{<p>Pediatric cancers exhibit complex evolutionary dynamics driven by genetic instability, clonal selection, epigenetic reprogramming, and microenvironmental interactions. Tumor evolution is typically characterized by branching phylogenies, where subclones with unique genetic profiles emerge at different locations and time points. Partly as a result of this diversity, advanced cancers often develop resistance to multiple therapies, complicating treatment strategies. This review explores recurrent themes in clonal evolution across childhood cancers as well as evolution-inspired strategies to counter treatment resistance. A model of dynamic decision making is suggested to accommodate emerging methods for monitoring shifts in a cancer's clonal landscape and the widening repertoire of precision drugs. A larger drug toolbox will allow for more sophisticated evolutionary stratagems to cure or stabilize cancer, using methods such as adaptive therapy, extinction therapy, and reflexive control therapies. However, there are also inherent limits in predicting and controlling cancer evolution- emphasizing the need for early detection, particularly in the setting of predicting relapse, which disproportionately contributes to cancer related mortality in childhood. Understanding the evolutionary trajectories of pediatric cancers can inform more effective, personalized treatment protocols, ultimately enhancing survival rates and quality of life for young patients.</p>}},
  author       = {{Karlsson, Jenny and Briggs, Mayen and Vedi, Aditi and Gisselsson, David}},
  issn         = {{1044-579X}},
  keywords     = {{Childhood cancer; Evolution; Evolutionary therapy; Genetic instability; Pediatric cancer; Selection}},
  language     = {{eng}},
  pages        = {{121--134}},
  publisher    = {{Academic Press}},
  series       = {{Seminars in Cancer Biology}},
  title        = {{Clonal evolution and therapy resistance in the era of precision cancer medicine : evolutionary trajectories in pediatric cancer}},
  url          = {{http://dx.doi.org/10.1016/j.semcancer.2025.10.001}},
  doi          = {{10.1016/j.semcancer.2025.10.001}},
  volume       = {{116}},
  year         = {{2025}},
}