Targeting PI3K/AKT/mTOR Pathway in Breast Cancer: From Biology to Clinical Challenges

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Breast cancer (BC) remains a leading cause of cancer death in women globally.
• Despite advancements, modest clinical benefits are observed with some new BC treatments.
• Mutations in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway occur in 20-40% of BC cases.

Purpose of the Study:

• To review the critical role of PI3K/AKT/mTOR pathway mutations in various breast cancer subtypes.
• To elucidate the impact of these mutations on clinical outcomes and treatment efficacy.
• To emphasize the need for enhanced understanding of the PI3K/AKT/mTOR pathway for personalized medicine.

Main Methods:

• Literature review focusing on PI3K/AKT/mTOR pathway mutations in breast cancer.
• Analysis of studies correlating pathway mutations with tumor behavior and treatment response.
• Synthesis of current knowledge on PI3K-mTORC1/C2 mutations across different BC subtypes.

Main Results:

• PI3K/AKT/mTOR pathway mutations are significantly associated with aggressive tumor behavior in breast cancer.
• These mutations contribute to resistance against established and emerging breast cancer therapies.
• The frequency and impact of these mutations vary across distinct breast cancer subtypes.

Conclusions:

• Targeting the PI3K/AKT/mTOR pathway presents a promising strategy for overcoming treatment resistance in breast cancer.
• A comprehensive understanding of PI3K-mTORC1/C2 mutations is essential for advancing personalized breast cancer therapy.
• Integrating tumor biology insights into treatment paradigms is key for the precision medicine era in breast cancer care.