Linoleic Acid, Seed Oils, mTOR & Breast Cancer | Nikos Koundouros & John Blenis | 229

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May 15, 2025

Nikos Koundouros, a postdoctoral fellow at Weill Cornell Medicine, joins John Blenis, a prominent pharmacology professor, to unravel how omega-6 fatty acids like linoleic acid may drive triple-negative breast cancer by activating the mTOR pathway. They discuss the critical role of the FABP5 protein, uniquely enhancing cancer cell sensitivity to these fats. The conversation reveals alarming shifts in modern diets, emphasizing the need for tailored nutrition approaches based on genetic variations and cancer subtypes to improve health outcomes.

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INSIGHT

mTOR is the Cell's Brain

mTOR acts as the brain of the cell, sensing nutrients and regulating growth.
Dysregulated mTOR leads to uncontrolled anabolism contributing to cancer development.

INSIGHT

Cancer Boosts Nutrient Uptake

Cancer cells enhance nutrient uptake by increasing transporter expression to fuel growth.
Genetic mutations can amplify mTOR signaling to sustain growth even under low nutrient conditions.

INSIGHT

Triple Negative Breast Cancer Explained

Triple-negative breast cancers lack estrogen, progesterone, and HER2 receptors.
They are more aggressive and lack targeted therapies, making treatment challenging.

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Episode Summary: New research on how dietary fats, particularly omega-6 fatty acids like linoleic acid, influence triple-negative breast cancer progression by activating the mTOR pathway, a key regulator of cell growth; role of the FABP5 protein in enhancing cancer cells’ sensitivity to omega-6 fats; differences between breast cancer subtypes; broader implications of dietary balance for health.

About the guest: John Blenis, PhD is a Professor of Pharmacology at the Meyer Cancer Center at Weill Cornell Medicine. Nikos Koundouros, PhD is a postdoctoral fellow in Blenis’ lab.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Transcript and other information on Substack.

Key Points:

mTOR pathway acts as a cellular “brain,” sensing nutrients like amino acids, glucose, and fats to regulate growth. Its dysregulation can drive cancer.
High dietary omega-6 fatty acids, like linoleic acid found in seed oils, can fuel triple-negative breast cancer growth by activating mTOR.
FABP5, a lipid chaperone protein, is overexpressed in triple-negative breast cancer, making these tumors more sensitive to omega-6 fats, suggesting its potential as a therapeutic target.
Modern diets with high omega-6 to omega-3 ratios disrupt inflammation balance, unlike historical 1:1 ratios, potentially increasing cancer risk.
Genetic variations and cancer subtypes highlight the need for tailored dietary recommendations, as blanket nutrition advice may not suit all patients.
While omega-6 fats exacerbate existing triple-negative breast cancer, their role in initiating cancer remains unclear, requiring further study.
High omega-6 intake may influence other cancers (e.g., prostate, colon) and chronic diseases like obesity, linked to FABP5 and inflammation.

Related episode:

M&M 200: Dietary Fats & Seed Oils in Inflamma

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