Identification of FDA-approved drugs targeting breast cancer stem cells along with biomarkers of sensitivity

Poornima Bhat-Nakshatri, Chirayu P. Goswami, Sunil Badve, George W. Sledge, Harikrishna Nakshatri

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Recently developed genomics-based tools are allowing repositioning of Food and Drug Administration (FDA)-approved drugs as cancer treatments, which were employed to identify drugs that target cancer stem cells (CSCs) of breast cancer. Gene expression datasets of CSCs from six studies were subjected to connectivity map to identify drugs that may ameliorate gene expression patterns unique to CSCs. All-trans retinoic acid (ATRA) was negatively connected with gene expression in CSCs. ATRA reduced mammosphere-forming ability of a subset of breast cancer cells, which correlated with induction of apoptosis, reduced expression of SOX2 but elevated expression of its antagonist CDX2. SOX2/CDX2 ratio had prognostic relevance in CSC-enriched breast cancers. K-ras mutant breast cancer cell line enriched for CSCs was resistant to ATRA, which was reversed by MAP kinase inhibitors. Thus, ATRA alone or in combination can be tested for efficacy using SOX2, CDX2, and K-ras mutation/MAPK activation status as biomarkers of response.

Original languageEnglish
Article number2530
JournalScientific Reports
Volume3
DOIs
StatePublished - 2013

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Neoplastic Stem Cells
United States Food and Drug Administration
Drug Delivery Systems
Biomarkers
Breast Neoplasms
Tretinoin
Gene Expression
Pharmaceutical Preparations
Genomics
Phosphotransferases
Apoptosis
Cell Line
Mutation
Neoplasms

ASJC Scopus subject areas

  • General
  • Medicine(all)

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Identification of FDA-approved drugs targeting breast cancer stem cells along with biomarkers of sensitivity. / Bhat-Nakshatri, Poornima; Goswami, Chirayu P.; Badve, Sunil; Sledge, George W.; Nakshatri, Harikrishna.

In: Scientific Reports, Vol. 3, 2530, 2013.

Research output: Contribution to journalArticle

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