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Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers

Samar Alsafadi1, Caroline Even, Coralie Falet

  • 1INSERM U981 "Identification of molecular predictors and new targets for cancer treatment", Gustave Roussy Cancer Institute, Villejuif, France.

Clinical Breast Cancer
|July 9, 2013
PubMed
Abstract

Insights

Breast cancers with RARA gene amplification may respond to retinoic acid derivatives. This finding suggests a new therapeutic strategy for specific breast cancer subtypes, warranting further clinical investigation.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Molecular segmentation of breast cancer aids in identifying patient subgroups sensitive to targeted therapies.
  • A patient with resistant HER2-overexpressing breast cancer and acute promyelocytic leukemia showed tumor response to retinoic acid, arsenic, and aracytin.

Observation:

  • Retinoic acid receptor alpha (RARA) was gained or amplified in 27% of HER2-positive and 13% of HER2-negative breast cancer samples.
  • RARA can be coamplified with HER2, and copy number changes correlate with its mRNA expression.
  • All-trans-retinoic acid (ATRA) induced apoptosis and reduced cell viability in RARA-amplified breast cancer cell lines.

Findings:

  • RARA amplification is associated with sensitivity to all-trans-retinoic acid (ATRA) in breast cancer.
  • ATRA-induced apoptosis in RARA-amplified cells involves increased CASP1 and IRF1 expression.
  • The study identified a potential predictive biomarker for retinoic acid therapy in breast cancer.

Implications:

  • Breast cancers with RARA amplifications represent a potential target for retinoic acid-based therapies.
  • This research may lead to novel treatment strategies for specific breast cancer populations.
  • A phase II clinical trial is planned to validate these findings in patients.
Keywords:
All-trans-retinoic acidCoamplificationHER2IRF1RARA

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