Metabolic Reprogramming in Triple-Negative Breast Cancer

Abstract

Metabolic reprogramming is an emerging hallmark of cancer cells, in which cancer cells exhibit distinct metabolic phenotypes to fuel their proliferation and progression. The significant advancements made in the area of metabolic reprogramming make possible new strategies for overcoming malignant cancer, including triple-negative breast cancer. Triple-negative breast cancer (TNBC) is associated with high histologic grade, aggressive phenotype, and poor prognosis. Even though triple-negative breast cancer patients benefit from standard chemotherapy, they still face high recurrence rates and are more likely to develop resistance to chemotherapeutic drugs. Therefore, there is an urgent need to explore vulnerabilities of triple-negative breast cancer and develop novel therapeutic drugs to improve clinical outcomes for triple-negative breast cancer patients. Metabolic reprogramming may provide promising therapeutic targets for the treatment of triple-negative breast cancer. In this paper, we primarily discuss how triple-negative breast cancer cells reprogram their metabolic phenotype and that of stromal cells in the microenvironment to survive under nutrient-poor conditions. Considering that metastasis and chemoresistance are the main contributors to mortality in triple-negative breast cancer patients, we also focus on the role of metabolic adaption in mediating metastasis and chemoresistance of triple-negative breast cancer tumors.

Targeting Glucose Metabolism to Overcome Resistance to Anticancer Chemotherapy in Breast Cancer

“…Additionally, HK2 and phosphofructokinase (PFK-L) status indicate the risk of relapse, aggressiveness, and poor prognosis in BC patients [ 37 , 38 ]. A review by Sun X et al [ 39 ] discusses various glycolytic enzymes and other metabolic pathways dysregulated in TNBC and the metabolic adaptations in metastasis and resistance. Earlier observations are in agreement with proteomic profiling of BC cells, revealed that most of the proteins overexpressed belonged to the glycolytic pathway [ 40 ].…”

“…Increased glucose utilization, activated glycolysis driven by oncogenic signaling to derive energy leading to lactate accumulation in cancer cells can occur even in the presence of oxygen. Concerning the glucose transporters (GLUT-1), the expression was higher in TNBC (basal-like) than in non-TNBC [ 39 ]. Frequently, GLUT-1 and GLUT-3 are upregulated in BC cell lines MDA-MB-435 and MDA-MB-231 [ 71 ].…”

Cancer-associated adipocytes: emerging supporters in breast cancer

“…Metabolic reprogramming, generally categorized as an emerging hallmark of cancer, is hijacked by BC to meet bioenergetic and biosynthetic demands, the redox balance maintenance, and cell proliferation [64]. The metabolic processes of BC and normal breast tissue are quite different in the aspect of glycolysis, tricarboxylic acid cycle, amino acids, nucleotides and/or lipid metabolism [65].…”

Role of GPX4-Mediated Ferroptosis in the Sensitivity of Triple Negative Breast Cancer Cells to Gefitinib

“…Triple-negative breast cancer (TNBC) accounts for about 20% of BC cases [2]. TNBC is a distinct subtype of BC characterized by aggressive phenotype, high recurrence rates, high visceral metastasis rate, and worse outcomes [3][4][5]. Molecular heterogeneity is prominent in the TNBC subtype, and is re ected by the obvious prognostic and patient's sensitivity to chemotherapy treatment, which is the only available systemic therapy currently [1].…”

“…Molecular heterogeneity is prominent in the TNBC subtype, and is re ected by the obvious prognostic and patient's sensitivity to chemotherapy treatment, which is the only available systemic therapy currently [1]. Although TNBC patients bene t from standard chemotherapy, they still face a high recurrence rate and a high possibility of drug resistance, leaving TNBC a major challenge in the clinic [4,6]. Clinical trial data show that ge tinib is well tolerated in patients with a wide range of tumor types [7].…”