This conceptual review explores how the Warburg effect—characterized by cancer cells favoring aerobic glycolysis over oxidative phosphorylation—intersects with the established hallmarks of cancer. The authors argue that this metabolic reprogramming is not merely a consequence but a driver of tumorigenesis. The shift to glycolysis results in reduced ATP yield, compelling
This 2014 prospective case series evaluated the safety and potential efficacy of a metabolic therapy regimen in 10 patients with advanced, chemoresistant metastatic cancers. The treatment combined intravenous alpha-lipoic acid (600 mg), oral hydroxycitrate (500 mg three times daily), and low-dose naltrexone (5 mg at bedtime). Patients included those with
This 2022 review explores the complex role of metformin, a widely used antidiabetic agent, in cancer therapy. Metformin activates the AMPK pathway and inhibits mitochondrial complex I, leading to reduced ATP production and downstream inhibition of mTOR and PI3K/AKT signaling pathways. These actions result in decreased tumor cell proliferation and
This 2015 news article in Science discusses findings from a study by Yun et al., which demonstrated that high-dose vitamin C selectively kills colorectal cancer cells harboring KRAS or BRAF mutations. The mechanism involves vitamin C entering cancer cells as dehydroascorbic acid (DHA) via GLUT1 transporters. Inside the cell, DHA
This 2017 review explores targeting the Warburg effect—a metabolic hallmark where cancer cells favor glycolysis over oxidative phosphorylation, leading to an acidic tumor microenvironment. The authors propose a therapeutic strategy combining metabolic modulators (e.g., dichloroacetate, metformin) and pH regulators to disrupt cancer cell metabolism and restore pH balance. Preclinical studies
This Phase I clinical trial evaluated the safety and efficacy of methioninase (METase) and recombinant methioninase (rMETase) in depleting serum methionine (MET) levels in high-stage cancer patients. MET dependence is a metabolic vulnerability in cancer cells, making MET depletion a potential therapeutic strategy. Three patients received non-recombinant METase, showing significant
This expert commentary by Barry Halliwell analyzes and contextualizes the findings from Ghanem et al., who reported that high-dose ascorbate (vitamin C) selectively induces death in breast cancer cells through redox imbalance and metabolic disruption. The mechanism involves increased oxidative stress, mitochondrial dysfunction, ATP depletion, and a shift in cellular
This 2015 review explores the diverse roles of sirtuins (SIRT1–SIRT7), a family of NAD⁺-dependent enzymes, in cancer biology. Sirtuins influence key processes such as metabolism, DNA repair, chromatin remodeling, and the tumor microenvironment. For instance, SIRT6 acts as a co-repressor for HIF1α, MYC, and NF-κB, thereby regulating cancer metabolism and
This review discusses the potential benefits of combining methionine restriction with methylation-axis blockade to target methionine addiction in cancer cells. By inhibiting methionine metabolism and blocking methylation processes, this approach reduces tumor growth and enhances the effectiveness of existing cancer treatments. The combination strategy holds promise for improving cancer therapy,
This review introduces the Mitochondrial-Stem Cell Connection (MSCC) hypothesis, suggesting that chronic oxidative phosphorylation (OxPhos) insufficiency in stem cells leads to the formation of cancer stem cells (CSCs) and drives tumorigenesis. The hypothesis explains metabolic alterations in cancer, where cells compensate for OxPhos deficiency by upregulating glycolysis and glutaminolysis. Dysfunctional
