Hormone receptor-positive, HER2-negative breast cancer is the most common subtype of breast cancer. While treatments have improved significantly over the years, many patients eventually develop resistance to standard therapies, allowing cancer to continue growing despite treatment.

Researchers have increasingly focused on a pathway known as PI3K/AKT/mTOR/PTEN, which plays a critical role in cancer growth and survival. New therapies targeting this pathway are creating additional treatment options and helping move breast cancer care toward a more personalized future.

Why the PI3K Pathway Matters

The PI3K/AKT/mTOR pathway acts as one of the body’s major growth-regulating systems.

Under normal conditions, it helps control:

  • Cell growth
  • Energy use
  • Cell survival
  • Protein production
  • Cell division

In many breast cancers, mutations cause this pathway to become overactive. When this happens, cancer cells can continue growing and dividing even when treatments are designed to stop them.

Researchers have found that abnormalities involving PI3K, AKT, mTOR, and PTEN are among the most common molecular changes seen in hormone receptor-positive breast cancer.

How Targeted Therapies Work

Targeted therapies are designed to interfere with specific molecular pathways that cancer cells rely on. Targeted means that the specifics related to the type of tumor can be targeted.

Rather than attacking all rapidly dividing cells like traditional chemotherapy, these drugs focus on particular abnormalities that help drive tumor growth.

This targeted approach can:

  • Slow cancer progression
  • Improve treatment response
  • Delay resistance
  • Preserve healthy tissue

Several therapies targeting different parts of the PI3K pathway are already being used in clinical practice, while others remain under investigation.

A Growing Number of Treatment Options

Researchers continue to develop new drugs that target:

  • PI3K mutations
  • AKT signaling
  • mTOR activation
  • PTEN-related abnormalities

These therapies are particularly important because many patients eventually develop resistance to hormone therapy alone.

By targeting additional growth pathways, doctors may be able to extend treatment effectiveness and improve long-term outcomes.

The Future of Precision Breast Cancer Care

One of the most important developments in modern oncology is the ability to match treatments to specific genetic abnormalities.

Molecular testing can help identify which patients are most likely to benefit from targeted therapies aimed at the PI3K pathway.

As researchers continue to learn more about the biology of breast cancer, treatment is becoming increasingly individualized. The goal is to select therapies based on the unique characteristics of each patient’s tumor rather than relying on a one-size-fits-all approach.

Source

Vrdoljak E, et al. New Emerging Therapies Targeting PI3K/AKT/mTOR/PTEN Pathway in Hormonal Receptor-Positive and HER2-Negative Breast Cancer—Current State and Molecular Pathology Perspective. Cancers (Basel). 2025;17(1):16. Accessed by: https://www.mdpi.com/2072-6694/17/1/16

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