Understanding Lipid Metabolism in Breast Cancer and Its Impact on Treatment

Medical News: A New Perspective on Breast Cancer
Breast cancer remains the most common cancer affecting women worldwide. Despite numerous advances in treatment, researchers are still uncovering new ways to understand the disease. One key focus is lipid metabolism, which refers to how cancer cells use fats to fuel their growth. Scientists from Peking Union Medical College Hospital and Tsinghua University in China have explored how changes in lipid metabolism impact breast cancer progression and potential treatments.


Understanding Lipid Metabolism in Breast Cancer and Its Impact on Treatment

This Medical News report highlights key findings from their study, showing that lipid metabolism is not just a side effect of cancer but an essential part of how breast tumors develop and survive. These discoveries could lead to new treatment options and better patient outcomes.
 
How Lipid Metabolism Changes in Breast Cancer
Healthy cells rely on a balanced supply of lipids, mainly obtained from the diet. However, cancer cells often alter their metabolism to create and store more lipids than normal cells. This change allows tumors to grow rapidly and resist damage from the immune system.
 
One significant finding from the study is that breast cancer cells increase de novo fatty acid synthesis, which means they produce their own fats instead of relying on external sources. Researchers found that key enzymes such as ATP citrate lyase (ACLY), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FASN) are highly active in breast cancer cells. These enzymes help tumors generate the fats they need to thrive.
 
Additionally, the study highlighted that saturated and monounsaturated fatty acids are the primary lipids produced by breast cancer cells, while polyunsaturated fatty acids (PUFAs) are scarce. The low PUFA levels help cancer cells avoid oxidative stress, a process that could otherwise lead to their destruction.
 
Lipid Metabolism and Drug Resistance
Another critical discovery is that lipid metabolism plays a role in making breast cancer cells resistant to chemotherapy and other treatments. Researchers found that high levels of ACLY are associated with worse clinical outcomes and resistance to multiple anti-cancer drugs. In particular, ACLY overexpression increases the production of Snail protein, a factor that helps cancer cells evade treatments and promotes their spread.
 
Similarly, the enzyme FASN was found to be highly expressed in about 70% of patients with triple-negative breast cancer (TNBC), a particularly aggressive form of the disease. This suggests that targeting FASN could be a potential treatment strategy for TNBC patients.
 
The Role of Lipid Metabolism in the Immune System
The study also explored how lipid metabolism affects the immune system’s ability to fight cancer. Researchers found that myeloid-derived suppressor cells (MDSCs), a type of immune cell that weakens the body’s defense against cancer, rely on fatty acid metabolism to function. Tumor cells release signals that enh ance fat absorption and oxidation in MDSCs, making them more effective at suppressing immune responses.
 
Additionally, lipid metabolism was found to influence immune checkpoints, which are molecules that help cancer cells evade immune attacks. The study showed that patients with high fat mass index (FMI) had significantly higher levels of immune checkpoint proteins such as PD-1, PD-L1, and CTLA-4, suggesting a direct link between lipid metabolism and immune evasion in breast cancer.
 
Lipid Biomarkers for Breast Cancer Diagnosis
Researchers also identified potential lipid-based biomarkers that could improve breast cancer diagnosis and prognosis. They found that specific lipid profiles in the blood could help predict disease progression. For example, increased levels of triglycerides and high-density lipoprotein (HDL) were associated with worse survival outcomes.
 
In addition to lipid levels, enzymes involved in lipid metabolism could serve as biomarkers. For instance, high FASN expression was linked to an increased risk of brain metastasis in breast cancer patients. Another study classified TNBC into different metabolic subtypes based on lipid production, which could help personalize treatment strategies.
 
Targeting Lipid Metabolism for Treatment
Given the importance of lipid metabolism in breast cancer, scientists are investigating potential treatments that target these metabolic pathways. Some promising approaches include:
 
-ACLY Inhibitors: Blocking ACLY has been shown to reduce tumor growth and enhance the effectiveness of chemotherapy. Some ACLY inhibitors, such as hydroxycitric acid (HCA), have demonstrated potential in reversing drug resistance in breast cancer cells.
 
-FASN Inhibitors: Drugs that target FASN have shown promise in slowing cancer growth, particularly in TNBC patients. Some clinical trials are testing these inhibitors in combination with other cancer treatments.
 
-Fatty Acid Oxidation (FAO) Inhibitors: Blocking FAO, a process that provides energy to cancer cells, could weaken tumors and make them more responsive to immunotherapy. Some studies suggest that FAO inhibitors can improve the effectiveness of PD-1 checkpoint blockade treatments.
 
-Lipid-Based Immunotherapy: Given the link between lipid metabolism and immune evasion, scientists are exploring therapies that disrupt fat absorption in immune cells to enhance the body’s natural defenses against cancer.
 
Conclusion
This study sheds new light on the critical role of lipid metabolism in breast cancer development, drug resistance, and immune system suppression. By targeting lipid-related pathways, researchers hope to develop more effective treatment options for breast cancer patients. The findings highlight the importance of integrating metabolic research with cancer therapy, potentially leading to breakthroughs that could improve survival rates and quality of life for patients.
 
As scientists continue to explore lipid metabolism in cancer, future treatments may focus on combining metabolic inhibitors with existing therapies to enhance their effectiveness. With further research, lipid-targeted therapies could become an essential part of personalized cancer treatment.
 
The study findings were published in the peer-reviewed journal: Cancers.
https://www.mdpi.com/2072-6694/17/4/650
 
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