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[PI3K/AKT pathway activation and therapeutic consequences in breast cancer]

Judit Olasz1, Zoltán Doleschall1, Zsuzsanna Dunai1

  • 1Országos Onkológiai Intézet, Budapest, Hungary. olasz@oncol.hu.

Magyar Onkologia
|December 15, 2015
PubMed

Insights

This study investigates PIK3CA mutations and PTEN loss in breast cancer, finding elevated PI3K/AKT pathway activity in most tumors. PTEN loss may drive proliferation via FGF signaling, suggesting FGF-2 and FGFR1 as potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Context:

  • The phosphatidylinositol-3-kinase/AKT (PI3K/AKT) pathway is frequently dysregulated in breast cancer.
  • Mechanisms include PI3K catalytic subunit alpha (PIK3CA) mutations and loss of phosphatase and tensin homolog (PTEN).
  • Hyperactivated PI3K/AKT signaling contributes to resistance against endocrine and trastuzumab therapies.

Purpose:

  • To identify PIK3CA mutations and mechanisms of PTEN loss in breast cancer.
  • To assess the therapeutic consequences of these alterations.
  • To identify potential therapeutic targets associated with PTEN loss.

Summary:

  • Sixty-nine primary breast cancer samples (ER+/PR+/HER2-, HER2+, and triple-negative) were analyzed for PTEN mRNA levels, mutations, allelic loss, and promoter hypermethylation.
  • Elevated PI3K/AKT pathway activity was observed in 68% of triple-negative, 45% of ER+/PR+, and 45% of HER2+ tumors.
  • PTEN loss was prevalent in triple-negative and HER2+ tumors, while PTEN loss and PI3K activation were equally represented in ER+/PR+ cancers.

Impact:

  • PTEN deficiency in cell lines correlated with increased fibroblast growth factor 2 (FGF2)/FGFR1 pathway signaling.
  • This suggests that PTEN loss may enhance autocrine FGF signaling, promoting cancer cell proliferation.
  • FGF-2 and FGFR1 are identified as potential therapeutic targets for PTEN-deficient breast cancers.

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