Integrating metabolic reprogramming and metabolic imaging to predict breast cancer therapeutic responses

Abstract

Metabolic reprogramming is not only an emerging hallmark of cancer, but also an essential regulator of cancer cell adaptation to the microenvironment. Metabolic imaging targeting metabolic signatures has been widely used for breast cancer diagnosis. However, limited implications have been explored for monitoring breast cancer therapy response, although metabolic plasticity is notably associated with therapy resistance. In this review, we focus on the metabolic alterations upon breast cancer therapy and their potential for evaluating breast cancer therapeutic responses. We summarize the metabolic network and regulatory changes upon breast cancer therapy in terms of cancer pathological and genetic differences and discuss the implications of metabolic imaging with various probes in selecting target beneficiaries for precision treatment. Key metabolic reprogramming of breast cancer in response to therapyReprogramming of glucose metabolism upon breast cancer therapy Drug-resistant breast cancer cells are able to reprogram glucose metabolism to adapt to the stress induced by drug treatment (Figure 1). For example, breast cancer cells resistant to lapatinib, a dual inhibitor of dermal growth factor receptor (EGFR) and HER2, recover the Highlights Reprogramming of metabolic pathways is pivotal for the adaptation and resistance to antitumor treatments in breast cancer.Metabolic changes upon treatment are superior to single timepoint metabolic signals in monitoring breast cancer therapeutic response.Cancer genetic and metabolic heterogeneity need to be fully integrated to precisely predict breast cancer response to different treatments.Metabolic imaging guided usage of anticancer drugs is critical for precise treatment in breast cancer.

Nucleotide metabolism: a pan-cancer metabolic dependency

“…For preclinical animal studies, metabolomic profiling of tumour tissue harvested at necropsy is a suitable alternative. Metabolic imaging modalities that enable tissue localization of exogenous metabolites, such as PET tracing of 18 F-labelled metabolites and MRI tracing of 13 C-labelled metabolites, represent another powerful tool to characterize the tumour and systemic host response to nucleotide synthesis inhibitors 156,157 .…”

Single‐cell transcriptome sequencing of B‐cell heterogeneity and tertiary lymphoid structure predicts breast cancer prognosis and neoadjuvant therapy efficacy

“…To our astonishment, TLS‐positive and TLS‐negative immune cells had entirely different metabolic pathways (Figure 7C). The tricarboxylic acid cycle (TCA cycle), glycolysis, and fatty acid production were all significantly increased in TLS‐negative tumours, and activation of these metabolic pathways is assumed to be closely related to carcinogenesis, progression and drug resistance 43 . We concentrated on the TCA cycle, glycolysis, fatty acid biosynthesis, oxidative phosphorylation and amino acid metabolism in BC immune cells to further investigate the metabolic differences in various states of TLSs (Figure 7D), as metabolic reprogramming grants cancer cells the ability to survive and proliferate, a key factor in tumour development 44 .…”

Metabolic Features of Saliva in Breast Cancer Patients

“…An increase in the activity of metabolic enzymes in saliva in breast cancer patients was an interesting fact (Table 2). An increase in the activity of LDH, the final enzyme of anaerobic glycolysis, was natural due to an increase in glycolysis along with a low efficiency of mitochondrial oxidation in breast cancer [49,50]. Several studies have shown that overexpression of ALP may be associated with metastatic processes in cancers, including breast cancer [51,52].…”