Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Transition Therapy: Tackling the Ecology of Tumour Phenotypic Plasticity

Version 1 : Received: 21 July 2020 / Approved: 23 July 2020 / Online: 23 July 2020 (10:36:22 CEST)

How to cite: Aguade, G.; Kauffman, S.; Sole, R. Transition Therapy: Tackling the Ecology of Tumour Phenotypic Plasticity. Preprints 2020, 2020070547 (doi: 10.20944/preprints202007.0547.v1). Aguade, G.; Kauffman, S.; Sole, R. Transition Therapy: Tackling the Ecology of Tumour Phenotypic Plasticity. Preprints 2020, 2020070547 (doi: 10.20944/preprints202007.0547.v1).

Abstract

Phenotypic switching in cancer cells has been found to be present across tumor types. Recent studies on Glioblastoma report a remarkably common architecture of four well-defined phenotypes coexisting within high levels of intra-tumour genetic heterogeneity. Tumours grown from any cell type recapitulate the original phenotypic composition. Similar dynamics have been shown to occur in breast cancer, melanoma and likely across further cancer types. Given the adaptive potential of phenotypic switching (PHS) strategies, understanding how it drives tumour evolution and how to break down these architectures is a major priority. Here we model the ecological dynamics behind PHS. The model is able to reproduce experimental results, and specific conditions for cancer progression and clearance reveal novel features of plastic tumours and its direct consequences on therapy resistance. Following our results we discuss \textit{transition} therapy as a novel scheme to target not only combined cytotoxicity but also the rates of phenotypic switching.

Subject Areas

Cancer ecology; phenotypic switching; epigenetic plasticity; combination therapies; transition therapy

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