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Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
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Identification of BRCA1 As a Potential Biomarker for Insulin-Like Growth Factor-1 Receptor Targeted Therapy in Breast

Tali Cohen-Sinai1,2, Zoya Cohen2, Haim Werner1,3

  • 1Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Frontiers in Endocrinology
|July 15, 2017
PubMed

Insights

BRCA1 mutations can impair the effectiveness of insulin-like growth factor-1 receptor (IGF1R) targeted therapies. This suggests BRCA1 status is a key biomarker for patient selection in IGF1R-directed cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biomarker Discovery

Background:

  • Insulin-like growth factor-1 receptor (IGF1R) is a promising therapeutic target in cancer treatment.
  • BRCA1, a tumor suppressor, regulates genes including IGF1R, with wild-type BRCA1 inhibiting IGF1R.
  • Predictive biomarkers for IGF1R-targeted therapies are crucial for patient selection.

Purpose of the Study:

  • To investigate if BRCA1 mutational status affects the efficacy of IGF1R-targeted therapies.
  • To evaluate the influence of BRCA1 status on IGF1R signaling inhibition by an IGF1R antibody.

Main Methods:

  • Utilized breast cancer cell lines with wild-type or mutant BRCA1.
  • Administered MK-0646, a monoclonal antibody targeting human IGF1R.
  • Assessed inhibition of IGF1R and downstream signaling phosphorylation.
  • Measured cell proliferation rates.

Main Results:

  • MK-0646's ability to inhibit IGF1R and downstream phosphorylation was reduced in mutant BRCA1 cells.
  • The antibody showed reduced inhibition of proliferation in mutant BRCA1-expressing cells compared to wild-type.
  • IGF1R inhibition by MK-0646 was less effective in the presence of BRCA1 mutations.

Conclusions:

  • BRCA1 mutational status significantly impacts the response to IGF1R-targeted therapies.
  • Patient selection for IGF1R-directed protocols should consider BRCA1 mutational status.
  • BRCA1 status may serve as a predictive biomarker for IGF1R-targeted cancer treatments.
Keywords:
BRCA1breast cancerinsulin-like growth factor-1insulin-like growth factor-1 receptortargeted therapy

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