Cancer Metabolism as a Therapeutic Target and Review of Interventions

Abstract

Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be affected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have an altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to target cancers metabolically by depriving them of glucose. In addition to dietary and lifestyle modifications which work on tumors metabolically, there are a panoply of nutritional supplements and repurposed drugs associated with cancer prevention and better treatment outcomes. These interventions and their evidentiary basis are covered in the latter half of this review to guide future cancer treatment.

Elevated N1-Acetylspermidine Levels in Doxorubicin-treated MCF-7 Cancer Cells: Histone Deacetylase 10 Inhibition with an N1-Acetylspermidine Mimetic

“…The heightened status of polyamines metabolism is linked to the tumor hallmarks including high proliferation and drug resistance in breast cancer cells [ 5 - 10 ]. Given the importance of polyamines in the metabolic-epigenomic landscape, acetylated polyamines such as N1-acetylspermidine and N1-acetylputrescine are thought to be intracellular indicators of drug-induced stress and death in cancer cell growth and proliferation [ 11 - 14 ].…”

“…In the context of various types of malignancies including breast cancer, altered levels of polyamines and their acetylated forms are noticed at the intracellular levels and extracellular environment including biological fluids such as serum and urine [ 5 - 14 ]. There is limited cell-based, in vivo, and clinical data on the nature and extent of the abundance of polyamines and their acetylated products including N1-acetylspermidine and N1-acetylputrescine in the context of drug-induced cell death in breast cancer cells.…”

“…Cancer cells have altered metabolisms compared to normal healthy cells and these alterations are responsible for their malignant properties [ 2 , 3 ]. Therefore, intracellular and extracellular profiles of metabolites such as polyamines, amino acids, peptides, vitamins, lipids, organic acids, carbohydrates, and nucleic acids are suggested to provide clues on metabolic adaptations during drug-induced stress in cancer cells, which accounts for their drug resistance [ 4 - 9 ]. Besides a basic understanding of cancer cell metabolism, profiling of intracellular and extracellular metabolites is considered an important approach for detection of cancer based on metabolite biomarkers.…”

MARCH5 promotes aerobic glycolysis to facilitate ovarian cancer progression via ubiquitinating MPC1

“…Metabolic reprogramming, characterized by increased aerobic glycolysis (also called Warburg effect) even in the presence of oxygen, has been known as a hallmark of malignancy, which is critical for cancer cells to support their energy demand and biomass synthesis required for hyperproliferation, invasion and metastasis [1,2]. However, the via ubiquitinating Mfn1, Drp1 and Fis1 [10].…”

Metabolomics combined with mathematical analysis reveals metabolic pathways specific to metastatic cancers

“…Intracellular metabolism of cancer is important not only for the survival of cancer cells but also in facilitating their invasion and metastasis potential ( 1 - 3 ). Cancer metabolism is known to differ from normal cellular metabolic processes, as exemplified by the Warburg effect ( 4 , 5 ). Metastases typically exhibit harsh environments characterized by reduced oxygen and nutrient availability compared to primary tumors ( 6 , 7 ), and thus require different metabolic pathways than those in primary tumors.…”