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

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TitlePhenotypic Plasticity, Bet-Hedging, and Androgen Independence in Prostate Cancer: Role of Non-Genetic Heterogeneity.
Publication TypeJournal Article
Year of Publication2018
AuthorsJolly, MKumar, Kulkarni, P, Weninger, K, Orban, J, Levine, H
JournalFront Oncol
Volume8
Pagination50
Date Published2018
ISSN2234-943X
Abstract

It 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.

DOI10.3389/fonc.2018.00050
Alternate JournalFront Oncol
PubMed ID29560343
PubMed Central IDPMC5845637
Grant ListR01 GM062154 / GM / NIGMS NIH HHS / United States
R21 CA181730 / CA / NCI NIH HHS / United States