Review provides overview of the current translational potential of metabolic and lipidomic biomarkers for predicting breast cancer prognosis and response to therapy.
Study: Lipidomics and metabolomics as potential biomarkers for breast cancer progression. Image Credit: Gorodenkoff/Shutterstock.com
A recent review in npj Metabolic Health and Disease discusses the potential of lipidomic and metabolic biomarkers to predict breast cancer prognosis and treatment response.
Background
Breast cancer is the most frequent cancer among United States women, with metastasis causing the most fatalities. Early identification and treatment are critical for preventing its spread.
Mammography and ultrasonography are popular detection methods; however, they have limited sensitivity and specificity. Advanced biomarkers could enhance breast cancer care since they can identify specific metabolomic and lipidomic changes linked to disease progression.
They may facilitate early detection, monitoring, and personalized treatments. This would improve therapy results, reduce overtreatment, and increase patient quality of life.
About the review
The present review highlights potential lipidomic and metabolic biomarkers for breast tumor progression.
Metabolomic markers of progressive breast cancer
Metabolomics is a tool for studying the metabolic mechanisms that influence cancer cell dynamics and development. It provides a thorough knowledge of how physiological circumstances interact with external stimuli and disorders, with metabolites serving as rapid indicators of pathological activity.
Cancer cells need glucose uptake and metabolic activity to grow and proliferate. Tumors alter nutrient consumption, with redox imbalance being a hallmark. Metabolomics enables the development of medications that target glucose transporters, such as phloretin and WZB117, as well as crucial glycolytic enzymes. Breast cancer cells use antioxidant mechanisms to maintain redox equilibrium and survival.
Cancer cells have different metabolic profiles than non-cancer cells. Amino acids like glutamate are critical for cell proliferation. They serve as precursors for biological pathways related to growth signaling. The proline dehydrogenase (PRODH) enzyme catalyzes proline, which promotes breast cancer metastasis. PRODH levels and proline catabolic activities are higher in metastatic cancers than in initial tumors. This suggests that they may be biomarkers or targets for progressing breast cancer.
Metabolites related to early breast cancer include lactate, acetoacetate, beta-hydroxybutyrate, pyruvate, glycoproteins, aspartate, alanine, taurine, mannose, and hypotaurine. In breast cancer, the levels of taurine, glycine, succinate, and lactate increase, and inositol decreases. High serum levels of beta-hydroxybutyrate and threonine link to fatigue and weight loss in breast cancer patients. Dysregulation of arachidonate 15-lipoxygenase-1 and asparagine synthetase pathways indicates cancer spreading to lymph nodes. Alterations in the methionine pathway, bile acid synthesis, and fatty and glucose metabolism occur in aggressive tumors.
Lipidomic markers of progressive breast cancer
Cancer cells need lipids like sterols, phospholipids, and glycerides for cell membrane formation, cell signaling, and energy storage. Breast cancer progression boosts lipogenesis and alters lipids to meet the higher metabolic needs and enable the rapid growth of tumor cells. Cancer cells use lipolysis and beta-oxidation to break down stored fatty acids and triglycerides for swift cellular division and invasion.
Biological pathways such as steroid hormone synthesis, eicosanoids, vitamins, and bile acids affect lipid metabolism. Lipid alterations meet the structural and energy requirements of growing cells. They also regulate stress responses, worsening cancer traits. An imbalance of choline-containing compounds correlates with tumor advancement.
Lipid remodeling shapes tumor microenvironments by compromising immune defense. Tumor cells secrete molecules that compromise immune function. Upregulated cholesterol, phospholipid, and fatty acid synthesis promote cell growth. Lipid remodeling interacts with tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs).
Myeloid cells lower immune responses in cancer. The types of myeloid cells involved are eosinophils, polymorphonuclear neutrophils, macrophages, dendritic cells, basophils, and megakaryocytes. TAMs enable the reprogramming of cells to pro-tumorigenic states. Lipids also help form blood vessels that supply nutrients to cancer cells.
Conclusions and future directions
The findings show that metabolic and lipidomic analysis can identify specific molecules and pathways related to breast cancer progression. Researchers can target these to develop personalized treatments. Such studies can analyze small amounts of various specimens, including lymph nodes, plasma, and urine, to profile breast cancer.
Challenges include the immediate freezing of samples, diet, gut microbiome, and medication influences, the need for advanced instruments, and separating metabolites from immune and cancer cells. High-carbohydrate diets increase plasma glucose, and high-fat diets raise lipids and cholesterol. Tumor cells can quickly rewire metabolic processes as they progress. This adds to the cancer’s metabolic diversity and aggressiveness.
The specificity and sensitivity of metabolomic and lipidomic markers and underlying mechanisms related to breast cancer progression remain unanswered. Further research should seek to integrate lipidomic and metabolomic data with genomic, proteomic, and transcriptomic data to improve the understanding of breast cancer progression. Additionally, researchers should assess changes in the cancer metabolome and lipidome during treatment.
The goal is to make profiling more accurate, faster, and cost-effective. While lipidomic and metabolomic analysis can identify biomarkers, few drugs target these metabolic abnormalities. This highlights the gap between finding biomarkers and using them in clinical practice.
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