Advances in Analyzing the Breast Cancer Lipidome and Its Relevance to Disease Progression and Treatment

Abstract

Abnormal lipid metabolism is common in breast cancer with the three main subtypes, hormone receptor (HR) positive, human epidermal growth factor 2 (HER2) positive, and triple negative, showing common and distinct lipid dependencies. A growing body of studies identify altered lipid metabolism as impacting breast cancer cell growth and survival, plasticity, drug resistance, and metastasis. Lipids are a class of nonpolar or polar (amphipathic) biomolecules that can be produced in cells via de novo synthesis or acquired from the microenvironment. The three main functions of cellular lipids are as essential components of membranes, signaling molecules, and nutrient storage. The use of mass spectrometry-based lipidomics to analyze the global cellular lipidome has become more prevalent in breast cancer research. In this review, we discuss current lipidomic methodologies, highlight recent breast cancer lipidomic studies and how these findings connect to disease progression and therapeutic development, and the potential use of lipidomics as a diagnostic tool in breast cancer. A better understanding of the breast cancer lipidome and how it changes during drug resistance and tumor progression will allow informed development of diagnostics and novel targeted therapies.

Lipid Metabolism Heterogeneity and Crosstalk with Mitochondria Functions Drive Breast Cancer Progression and Drug Resistance

“…Lipids are the main structural components of cell membrane compartment that also play a vital role as energy sources and signaling molecules. Dysregulated lipid metabolism pathways in breast cancer have received renewed interest, as oncogenic signaling and molecular heterogeneity regulate lipidomics and the progression of BC [ 17 ]. The key metabolic hallmarks of BC cells are alterations in fatty acid (FA) transport, uptake, de novo lipogenesis, storage and oxidation to generate ATP (adenosine triphosphate) ( Figure 2 ) [ 12 ].…”

Scientometric analysis of lipid metabolism in breast neoplasm: 2012–2021

“…As crucial biomolecules, lipids are not only the component of cell membranes but also signal transduction molecules and energy sources ( Bian et al, 2021 ; Ward et al, 2021 ; Batchuluun et al, 2022 ). An increasing number of studies have shown that lipid metabolism is abnormal in cancer ( Faubert et al, 2020 ; Snaebjornsson et al, 2020 ; Bian et al, 2021 ).…”

“…What is noteworthy is that breast cancer is closely related to lipid metabolism. Breast cancer is mainly divided into hormone receptor (HR) positive subtype, human epidermal growth factor 2 (HER2) positive subtype, and triple-negative subtype, showing different degrees of lipid dependence ( Ward et al, 2021 ). It has been identified that APOL4, NR1H3, and other genes related to lipid metabolism are independent prognostic markers of breast neoplasm and can predict overall survival in breast cancer patients ( Chang and Xing, 2022 ; Wang and Wang, 2022 ).…”

“…It has been identified that APOL4, NR1H3, and other genes related to lipid metabolism are independent prognostic markers of breast neoplasm and can predict overall survival in breast cancer patients ( Chang and Xing, 2022 ; Wang and Wang, 2022 ). Lipid metabolism is likely to be a breakthrough for targeted therapy of breast cancer ( Ward et al, 2021 ). The progress of lipidomics has strengthened the research on lipids of breast cancer, but metabolic drugs for breast cancer treatment are still undeveloped and need to be further studied ( Ward et al, 2021 ).…”

“…Lipid metabolism is likely to be a breakthrough for targeted therapy of breast cancer ( Ward et al, 2021 ). The progress of lipidomics has strengthened the research on lipids of breast cancer, but metabolic drugs for breast cancer treatment are still undeveloped and need to be further studied ( Ward et al, 2021 ). In conclusion, the study of lipid metabolism in breast cancer has significance in the treatment and prediction of survival.…”