Phenotypic Plasticity, Bet-Hedging, and Androgen Independence in Prostate Cancer: Role of Non-Genetic Heterogeneity

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dc.citation.articleNumber50
dc.citation.journalTitleFrontiers in Oncology
dc.citation.volumeNumber8
dc.contributor.authorJolly, Mohit Kumar
dc.contributor.authorKulkarni, Prakash
dc.contributor.authorWeninger, Keith
dc.contributor.authorOrban, John
dc.contributor.authorLevine, Herbert
dc.date.accessioned2019-01-24T16:08:01Z
dc.date.available2019-01-24T16:08:01Z
dc.date.issued2018
dc.description.abstractIt is well known that genetic mutations can drive drug resistance and lead to tumor relapse. Here, we focus on alternate mechanisms-those without mutations, such as phenotypic plasticity and stochastic cell-to-cell variability that can also evade drug attacks by giving rise to drug-tolerant persisters. The phenomenon of persistence has been well-studied in bacteria and has also recently garnered attention in cancer. We draw a parallel between bacterial persistence and resistance against androgen deprivation therapy in prostate cancer (PCa), the primary standard care for metastatic disease. We illustrate how phenotypic plasticity and consequent mutation-independent or non-genetic heterogeneity possibly driven by protein conformational dynamics can stochastically give rise to androgen independence in PCa, and suggest that dynamic phenotypic plasticity should be considered in devising therapeutic dosing strategies designed to treat and manage PCa.
dc.identifier.citationJolly, Mohit Kumar, Kulkarni, Prakash, Weninger, Keith, et al.. "Phenotypic Plasticity, Bet-Hedging, and Androgen Independence in Prostate Cancer: Role of Non-Genetic Heterogeneity." <i>Frontiers in Oncology,</i> 8, (2018) Frontiers: https://doi.org/10.3389/fonc.2018.00050.
dc.identifier.digitalfonc-08-00050
dc.identifier.doihttps://doi.org/10.3389/fonc.2018.00050
dc.identifier.urihttps://hdl.handle.net/1911/105127
dc.language.isoeng
dc.publisherFrontiers
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.keywordandrogen independence
dc.subject.keywordbet-hedging
dc.subject.keywordintermittent androgen therapy
dc.subject.keywordnon-genetic heterogeneity
dc.subject.keywordphenotypic plasticity
dc.subject.keywordstochasticity
dc.titlePhenotypic Plasticity, Bet-Hedging, and Androgen Independence in Prostate Cancer: Role of Non-Genetic Heterogeneity
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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