title: Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions.
abstract: Ideal oncology drugs would be curative after a short treatment course if they could eliminate epithelium-originated carcinomas at their non-invasive, pre-malignant stages. Such ideal molecules, which are expected to molecularly abrogate all the instrumental mechanisms acquired by migrating cancer stem cells (CSCs) to by-pass tumour suppressor barriers, might already exist. We here illustrate how system biology strategies for repositioning existing FDA-approved drugs may accelerate our therapeutic capacity to eliminate CSC traits in pre-invasive intraepithelial neoplasias. First, we describe a signalling network signature that overrides bioenergetics stress- and oncogene-induced senescence (OIS) phenomena in CSCs residing at pre-invasive lesions. Second, we functionally map the anti-malarial chloroquine and the anti-diabetic metformin ("old drugs") to their recently recognized CSC targets ("new uses") within the network. By discussing the preclinical efficacy of chloroquine and metformin to inhibiting the genesis and self-renewal of CSCs we finally underscore the expected translational impact of the "old drugs-new uses" repurposing strategy to open a new CSC-targeted chemoprevention era.
authors: Unit of Translational Research, Catalan Institute of Oncology-Girona, Avenida de Francia s/n, E-17007 Girona, Catalonia, Spain.
authors: Alejandro
authors: A
authors: Vazquez-Martin
authors: Eugeni
authors: E
authors: López-Bonetc
authors: Sílvia
authors: S
authors: Cufí
authors: Cristina
authors: C
authors: Oliveras-Ferraros
authors: Sonia
authors: S
authors: Del Barco
authors: Begoña
authors: B
authors: Martin-Castillo
authors: Javier A
authors: JA
authors: Menendez
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