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Scientific article
Open access
English

The human antigen R as an actionable super-hub within the network of cancer cell persistency and plasticity

ContributorsMerat, Rastineorcid
Published inTranslational oncology, vol. 35, 101722
Publication date2023-09
Abstract

In this perspective article, a clinically inspired phenotype-driven experimental approach is put forward to address the challenge of the adaptive response of solid cancers to small-molecule targeted therapies. A list of conditions is derived, including an experimental quantitative assessment of cell plasticity and an information theory-based detection of in vivo dependencies, for the discovery of post-transcriptional druggable mechanisms capable of preventing at multiple levels the emergence of plastic dedifferentiated slow-proliferating cells. The approach is illustrated by the author's own work in the example case of the adaptive response of BRAFV600-melanoma to BRAF inhibition. A bench-to-bedside and back to bench effort leads to a therapeutic strategy in which the inhibition of the baseline activity of the interferon-γ-activated inhibitor of translation (GAIT) complex, incriminated in the expression insufficiency of the RNA-binding protein HuR in a minority of cells, results in the suppression of the plastic, intermittently slow-proliferating cells involved in the adaptive response. A similar approach is recommended for the validation of other classes of mechanisms that we seek to modulate to overcome this complex challenge of modern cancer therapy.

eng
Keywords
  • Adaptive resistance
  • Cell plasticity
  • HuR
  • RNA-binding protein
  • Slow-cycling cell
  • Melanoma
Citation (ISO format)
MERAT, Rastine. The human antigen R as an actionable super-hub within the network of cancer cell persistency and plasticity. In: Translational oncology, 2023, vol. 35, p. 101722. doi: 10.1016/j.tranon.2023.101722
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ISSN of the journal1936-5233
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