Breast Cancer Recurrence After Treatment Linked to Fat Metabolism

Breast cancer is among the cancers with the greatest treatment advances in recent years; 5-year survival, expressing complete recovery, has reached %90. However, recurrence after treatment remains important. New research suggests that if breast cancer cells remain after treatment, their fat (lipid) metabolism differs. What does this mean?

Studies increasingly investigate factors associated with post-treatment recurrence, also called relapse. They generally aimed to understand changes in cancer cells’ energy-production pathways. A newly published study examined genetic profiles of “cells remaining after treatment” to understand factors related to recurrence. Two important features strengthen its scientific basis:

1. Genetic manipulation in mouse models produced cancer recurrence in the same way as in humans.
2. Using 3-dimensional organoids (organ-like structures), “cells remaining after treatment” were effectively isolated.

Genetic Analysis Showed That These Isolated Post-Treatment Residual Cells Metabolize Fat-Lipid Molecules Differently From Normal Cells.

Normally, reactive oxygen species (ROS) arise from aerobic respiration in our cells. Various mitochondrial enzymes neutralize them. Excess ROS can damage cellular DNA, potentially resulting in diseases such as heart failure, nervous system disorders, diabetes and cancer. The studied cells maintained high ROS levels, increasing the likelihood of DNA mutations that could cause recurrence. Similar fat-metabolism changes were observed when the same study was performed in human cancer cells.

So What Does This Study Mean for Cancer Treatment?

• Recurrence is an important factor making cancer treatment difficult. Detecting it in advance may allow preventive approaches to be developed.
• Cancer cell metabolism differs greatly from healthy cells. Cancer metabolic changes are associated with metastasis and cancer drug resistance.
• The importance of this study is discovering that recurrence is also linked to changes in “fat metabolism.”
• Identifying changes in cancer cell fat metabolism sheds light on developing targeted treatments.
• Researchers are trying to develop tests detecting fat molecules in blood or urine to identify recurrence at an “early stage.” Importantly, no such test is in clinical use; research continues at laboratory level. .

Further READING: Cancer Cell Metabolism: THE WARBURG EFFECT

Among cancer cells’ 10 fundamental characteristics is altering energy metabolism. Rapidly and uncontrollably multiplying cancer cells need large amounts of energy, so they change energy sources and pathways. Cancer metabolic changes were described by Nobel Prize-winning German physician Otto Heinrich Warburg and called the “Warburg Effect.” The figure below illustrates it.

Normal (differentiated/healthy) cells produce energy through different pathways in oxygenated and oxygenated environments. In oxygen, they perform aerobic respiration, generating energy. Without oxygen, they produce energy through “glycolysis,” generating lactic acid. This lactic acid causes muscle fatigue/pain after intense exercise.

Most tumor cells produce energy through glycolysis regardless of oxygen availability. Lactic acid consequently accumulates, creating an acidic environment. Cancer cell glycolysis rates are 200 times higher than normal cells.

Therefore, an acidic environment is a consequence of cancer, not its cause. Alkaline treatments cannot treat cancer and may initiate problems leading even to death

How Does the Warburg Effect Occur?

Mutations in cancer cells are thought to trigger the Warburg Effect. Damage to mitochondria, where aerobic respiration occurs, or low oxygen around tumor cells also causes cancer cells to keep mitochondrial genes inactive.

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• Targeting metastasis-initiating cancer cells through the newly discovered fatty acid receptor CD36