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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Targeted Metabolic Alterations in Prostate Cancer: A Promising Therapeutic Strategy
Zhanning Qu1,2, Feng Hao1, Zhaojun Li3
1College of Laboratory Medicine, Jilin Medical University, Jilin City, Jilin 132013, China.
Abstract:
The treatment of prostate cancer (PCa) remains a major challenge due to the development of resistance to androgen receptor (AR)-targeted therapies and paclitaxel-based chemotherapeutic agents, highlighting the need for novel therapeutic approaches. Unlike the majority of tumor cells that depend on aerobic glycolysis (the Warburg effect) for energy production, early stage PCa primarily utilizes oxidative phosphorylation (OXPHOS), while advanced-stage PCa shifts to aerobic glycolysis. Consequently, targeting metabolic alterations specific to PCa may represent a promising therapeutic strategy. This review initially delineates the glucose metabolism phenotype characteristic of healthy prostate cells as well as primary and metastatic PCa cells, which underpin the development and progression of the disease. Subsequently, it elaborates on the roles and mechanisms of inhibitors targeting key enzymes involved in glycolysis and the synthesis of OXPHOS in the context of PCa treatment. Finally, the review discusses inhibitors that concurrently target both glycolysis and OXPHOS, potentially mitigating the compensatory pathways that support cancer cell survival. Collectively, this review contributes to a deeper understanding of metabolic alterations in PCa and informs the ongoing development of therapeutic interventions.
Insights
Prostate cancer (PCa) cells alter their metabolism, shifting from oxidative phosphorylation (OXPHOS) to aerobic glycolysis. Targeting these metabolic pathways offers a promising strategy for novel PCa treatments.
Area of Science:
- Oncology
- Cancer Metabolism
- Biochemistry
Background:
- Prostate cancer (PCa) treatment faces challenges due to resistance to current therapies like androgen receptor (AR)-targeted drugs and chemotherapy.
- PCa exhibits distinct metabolic phenotypes: early stages rely on oxidative phosphorylation (OXPHOS), while advanced stages utilize aerobic glycolysis (Warburg effect).
Purpose of the Study:
- To review the glucose metabolism characteristics of healthy, primary, and metastatic PCa cells.
- To explore therapeutic strategies targeting metabolic alterations in PCa.
- To discuss inhibitors targeting glycolysis, OXPHOS, and combined pathways for PCa treatment.
Main Methods:
- Literature review of metabolic pathways in prostate cancer.
- Analysis of glucose metabolism phenotypes in different PCa stages.
- Examination of inhibitors targeting key enzymes in glycolysis and OXPHOS.
Main Results:
- PCa cells exhibit a metabolic shift from OXPHOS to aerobic glycolysis as the disease progresses.
- Specific enzymes in glycolysis and OXPHOS are crucial for PCa cell survival and progression.
- Inhibitors targeting these metabolic pathways show potential for PCa therapy.
Conclusions:
- Understanding PCa's metabolic reprogramming is crucial for developing effective treatments.
- Targeting both glycolysis and OXPHOS may overcome resistance and improve therapeutic outcomes.
- Metabolic interventions represent a promising avenue for novel prostate cancer therapies.
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