Lipidomics and metabolomics as potential biomarkers for breast cancer progression

Abstract

Breast cancer is the most prevalent cancer among women in the United States, representing ~30% of all new female cancer cases annually. For the year 2024, it is estimated that 310,720 new instances of invasive breast cancer will be diagnosed, and breast cancer will be responsible for over 42,000 deaths among women. Today, despite the availability of numerous treatments for breast cancer and its symptoms, most cancer-related deaths result from metastasis for which there is no treatment. This emphasizes the importance of early detection and treatment of breast cancer before it spreads. For initial detection and staging of breast cancer, clinicians routinely employ mammography and ultrasonography, which, while effective for broad screening, have limitations in sensitivity and specificity. Advanced biomarkers could significantly enhance the precision of early detection, enable more accurate monitoring of disease evolution, and facilitate the development of personalized treatment plans tailored to the specific molecular profile of each tumor. This would not only improve therapeutic outcomes, but also help in avoiding overtreatment and the associated side effects, thereby improving the quality of life for patients. Thus, the pursuit of novel biomarkers, potentially encompassing metabolomic and lipidomic signatures, is essential for advancing breast cancer diagnosis and treatment. In this brief review, we will provide an overview of the current translational potential of metabolic and lipidomic biomarkers for predicting breast cancer prognosis and response to therapy.

Fig. 1. Representative anti‐cancer drugs targeting carbon, glucose, and fatty acid metabolism.

A Carbon metabolism has revealed various targets of interest in the folate synthesis pathway. Metabolomic techniques have led to the development of drugs like methotrexate and capecitabine to target thymidylate synthase and methotrexate to target key enzyme dihydrofolate reductase (DHFR). B Glucose metabolism modulators target glucose transporters phloretin and WZB117 as well as key enzymes in the glycolytic pathway like inhibition of hexokinase 2 via Genistein-27 and Resveratrol^,. Within the same pathway, metabolomic techniques have further pioneered anti-cancer drugs targeting glucose 6 phosphate dehydrogenase (G6PD), like Polydatin which inhibits glycolysis, as well drugs targeting the conversion of pyruvate to lactate via the key enzyme lactate dehydrogenase (LDH) with Oxamate and FX11. C Fatty acid metabolism targets include Betulin which inhibits sterol regulatory element binding protein 1 (SREBP-1). At a synthesis level, key enzymes acetyl-CoA carboxylase is inhibited via Soraphen A and fatty-acid synthase by TVB-2640^,. Figure generated with BioRender.com.

Fig. 2. Clinical potential of lipidomic and metabolomic profiling in breast cancer.

As fine-needle aspirations are commonly performed on primary breast tumors and lymph node biopsies, it represents a novel sampling method that could be used to determine the metabolic and lipidomic profile of the tissues for comparison of profiles between primary tumor and progression to lymph nodes. Figure generated with BioRender.com.