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

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dc.citation.articleNumber50en_US
dc.citation.journalTitleFrontiers in Oncologyen_US
dc.citation.volumeNumber8en_US
dc.contributor.authorJolly, Mohit Kumaren_US
dc.contributor.authorKulkarni, Prakashen_US
dc.contributor.authorWeninger, Keithen_US
dc.contributor.authorOrban, Johnen_US
dc.contributor.authorLevine, Herberten_US
dc.date.accessioned2019-01-24T16:08:01Zen_US
dc.date.available2019-01-24T16:08:01Zen_US
dc.date.issued2018en_US
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.en_US
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.en_US
dc.identifier.digitalfonc-08-00050en_US
dc.identifier.doihttps://doi.org/10.3389/fonc.2018.00050en_US
dc.identifier.urihttps://hdl.handle.net/1911/105127en_US
dc.language.isoengen_US
dc.publisherFrontiersen_US
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.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.subject.keywordandrogen independenceen_US
dc.subject.keywordbet-hedgingen_US
dc.subject.keywordintermittent androgen therapyen_US
dc.subject.keywordnon-genetic heterogeneityen_US
dc.subject.keywordphenotypic plasticityen_US
dc.subject.keywordstochasticityen_US
dc.titlePhenotypic Plasticity, Bet-Hedging, and Androgen Independence in Prostate Cancer: Role of Non-Genetic Heterogeneityen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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