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Heritable genetic or epigenetic changes in cells are thought to drive tumor development, metastasis, and drug resistance. This essay discusses the possibility that nonheritable phenotypic variability contributes to the evolution of cancer, suggesting new approaches to treatment.
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Keywords {🔍}
variability, cells, resistance, drug, nonheritable, evolutionary, phenotypic, genetic, cellular, cancer, view, article, google, scholar, treatment, heritable, phenotype, adaptation, phenotypes, variants, cell, search, change, response, evolution, initial, state, protein, stochastic, fluctuations, variation, plos, arise, rate, resistant, binding, environment, populations, challenge, stress, shortrange, longrange, expression, environmental, carcinogenesis, challenges, synergism, epigenetic, progression, physiological,
Topics {✒️}
health grant gm087630 plos biol 10 plos biol 6 cookies plos open-access article distributed genetics 169 azt-3tc combination therapy hogge-baer visiting professorship complex evolutionary processes dynamical systems theory slow-cycling melanoma cells high-dimensional attractor states base “wild-type” strain long-range search play long-range search discover systems view �short-range search” occurs single-gene deletion strains �long-range search” occurs open problems nonheritable variability accelerates artificial systems short-range search spread drug therapy complex phenotypically b-cell lineage combination therapy altering ligand binding systems pharmacology drugs applied simultaneously simultaneously applied drugs complex process complex space stably heritable variants altered chromatin state nonheritable phenotypic variation preexisting genetic variation nonheritable cellular variation nonheritable phenotypic variants temporarily distinct subpopulation nonheritable phenotypic variability nonheritable variability initiate recent reviews discuss preexisting genetic variants nonheritable cellular variability histone-mediated alterations cookie policy preexisting heritable variants control nonheritable variability gene network dynamics
Questions {❓}
- But does genotype always come before phenotype in an evolutionary response [5]?
- But does it actually happen that way?
- But how important and widespread are the consequences of nonheritable variability?
- Do we need to think mainly about genetic variants, or does nonheritable variability initiate the key steps of carcinogenesis and resistance?
- F (2010) Cellular heterogeneity: do differences make a difference?
- G, Parry G (1982) How does the extracellular matrix direct gene expression?
- Given the phenotypic range expressed by a human cell through stochastic fluctuations and in response to different environments, how might one think about alternative treatment strategies?
- How can we reconcile the evidence for preexisting genetic variation with the observations on nonheritable phenotypic variability?
- How do such long-range shifts in phenotype arise and spread in populations in response to novel and sometimes extreme environmental challenge?
- How does the altered signaling state first arise?
- How does the evolving system of cancer tissues find novel phenotypes that improve competitive success and cause the spread of the tumor?
- How should the recent results on nonheritable variability in drug resistance be interpreted in relation to genetic variability?
- Should combination therapies be designed differently if the origin of resistance sometimes comes from nonheritable variability rather than preexisting genetic variants?
- W (2000) Undermining the Baldwin expediting effect: Does phenotypic plasticity accelerate evolution?
- When does the novel genetic change arise in an evolutionary step?
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- Leaflet
- Lightbox
- Modernizr
- Moment.js
- Underscore.js
- Video.js
- Vue.js
- Zoom.js
Emails and Hosting {✉️}
Mail Servers:
- mx.zoho.eu
- mx2.zoho.eu
- mx3.zoho.eu
Name Servers:
- josh.ns.cloudflare.com
- zita.ns.cloudflare.com
CDN Services {📦}
- Cloudflare
- Crossref