Metabolic changes in triple negative breast cancer-focus on aerobic glycolysis
J R Dev Arundhathi1, Sandeep R Mathur2, Ajay Gogia1
1Department of Medical Oncology, Dr BRA IRCH, AIIMS, New Delhi, 110029, India.
Abstract:
Among breast cancer subtypes, the triple negative breast cancer (TNBC) has the worst prognosis. In absence of any permitted targeted therapy, standard chemotherapy is the mainstay for TNBC treatment. Hence, there is a crucial need to identify potential druggable targets in TNBCs for its effective treatment. In recent times, metabolic reprogramming has emerged as cancer cells hallmark, wherein cancer cells display discrete metabolic phenotypes to fuel cell progression and metastasis. Altered glycolysis is one such phenotype, in which even in oxygen abundance majority of cancer cells harvest considerable amount of energy through elevated glycolytic-flux. In the present review, we attempt to summarize the role of key glycolytic enzymes i.e. HK, Hexokinase; PFK, Phosphofructokinase; PKM2, Pyruvate kinase isozyme type 2; and LDH, Lactate dehydrogenase in TNBCs, and possible therapeutic options presently available.
Insights
Triple negative breast cancer (TNBC) lacks targeted therapies. This review explores how altered glycolysis, involving key enzymes like Hexokinase (HK), fuels TNBC progression, and discusses potential therapeutic strategies.
Area of Science:
- Oncology
- Cancer Metabolism
- Biochemistry
Background:
- Triple negative breast cancer (TNBC) presents a poor prognosis.
- Current TNBC treatment relies on standard chemotherapy due to a lack of targeted therapies.
- Identifying novel druggable targets is critical for effective TNBC treatment.
Purpose of the Study:
- To review the role of key glycolytic enzymes in TNBC.
- To explore altered glycolysis as a metabolic hallmark in TNBC.
- To summarize potential therapeutic options targeting glycolysis in TNBC.
Main Methods:
- Literature review focusing on metabolic reprogramming in cancer.
- Analysis of the function of key glycolytic enzymes: Hexokinase (HK), Phosphofructokinase (PFK), Pyruvate kinase isozyme type 2 (PKM2), and Lactate dehydrogenase (LDH).
- Examination of therapeutic strategies targeting the glycolytic pathway in TNBC.
Main Results:
- Altered glycolysis, characterized by elevated glycolytic flux even in normoxia, is a key metabolic phenotype in TNBC.
- Specific glycolytic enzymes (HK, PFK, PKM2, LDH) play significant roles in fueling TNBC cell progression and metastasis.
- Targeting these enzymes presents potential therapeutic avenues for TNBC.
Conclusions:
- Metabolic reprogramming, particularly altered glycolysis, is a crucial aspect of TNBC.
- Key glycolytic enzymes are potential targets for novel therapeutic interventions in TNBC.
- Further research into targeting glycolysis may lead to improved TNBC treatment outcomes.
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