Stress-induced cellular adaptive strategies: Ancient evolutionarily conserved programs as new anticancer therapeutic targets

Despite the remarkable achievements of novel targeted anti‐cancer drugs, most therapies only produce remission for a limited time, resistance to treatment, and relapse, often being the ultimate outcome. Drug resistance is due to highly efficient adaptive strategies utilized by cancer cells. Exogenou...

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Veröffentlicht in:BioEssays Jg. 36; H. 6; S. 552 - 560
Hauptverfasser: Cipponi, Arcadi, Thomas, David M.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Blackwell Publishing Ltd 01.06.2014
Wiley Subscription Services, Inc
Schlagworte:
Adaptation, Biological
adaptive response
Animals
cancer
Cells - metabolism
Cells - pathology
Chemotherapy
Drug resistance
Evolution, Molecular
genomic instability
Humans
Medical research
Molecular Targeted Therapy
Neoplasms - pathology
Neoplasms - therapy
stress
Stress, Physiological
Subpopulations
Yeasts
stress
cancer
adaptive response
drug resistance
genomic instability
ISSN:0265-9247, 1521-1878, 1521-1878
Online-Zugang:Volltext
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Zusammenfassung:Despite the remarkable achievements of novel targeted anti‐cancer drugs, most therapies only produce remission for a limited time, resistance to treatment, and relapse, often being the ultimate outcome. Drug resistance is due to highly efficient adaptive strategies utilized by cancer cells. Exogenous and endogenous stress stimuli are known to induce first‐line responses, capable of re‐establishing cellular homeostasis and determining cell fate decisions. Cancer cells may also mount second‐line adaptive strategies, such as the mutator response. Hypermutable subpopulations of cells may expand under severe selective stress, thereby accelerating the emergence of adapted clones. As with first‐line protective responses, these strategies appear highly conserved, and are found in yeasts and bacteria. We hypothesize that evolutionarily conserved programs rheostatically regulate mutability in fluctuating environments, and contribute to drug resistance in cancer cells. Elucidating the conserved genetic and molecular mechanisms may present novel opportunities to increase the effectiveness of cancer therapies. Resistance to anticancer therapies is partly due to the mutagenic capacity of malignant cells, accelerating adaptation to selective pressures. Since similar phenomena have been observed in prokaryotes and primitive eukaryotes, we hypothesize that evolutionarily conserved mechanisms may regulate hypermutability in cancer cells in response to environmental stress, including drug therapy.
Bibliographie:ark:/67375/WNG-9SPCGCVM-N
istex:0949DADF7234625E24BC9A858624D8FFB35BFC92
ArticleID:BIES201300170
ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:0265-9247
1521-1878
1521-1878
DOI:10.1002/bies.201300170