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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.

SUBMITTER: Vazquez-Martin A

PROVIDER: S-EPMC3742095 | biostudies-literature | 2011 Aug-Oct

REPOSITORIES: biostudies-literature

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Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions.

Vazquez-Martin Alejandro A López-Bonetc Eugeni E Cufí Sílvia S Oliveras-Ferraros Cristina C Del Barco Sonia S Martin-Castillo Begoña B Menendez Javier A JA

Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 20110519 4-5

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 therapeuti ...[more]

PMID: 21600837

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Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions.

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Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions.

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