Cancer cells have been shown to have altered metabolism when compared to normal non-malignant cells. The Warburg effect describes a phenomenon in which cancer cells preferentially metabolize glucose by glycolysis, producing lactate as an end product, despite being the presence of oxygen. The phenomenon was first described by Otto Warburg in the 1920s, and has resurfaced as a controversial theory, with both supportive and opposing arguments. The biochemical aspects of the Warburg effect outline a strong explanation for the cause of cancer cell proliferation, by providing the biological requirements for a cell to grow. Studies have shown that pathways such as phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) as well as hypoxia inducible factor-1 (HIF-1) are central regulators of glycolysis, cancer metabolism and cancer cell proliferation. Studies have shown that PI3K signaling pathways have a role in many cellular processes such as metabolism, inflammation, cell survival, motility and cancer progression. Herein, the cellular aspects of the PI3K pathway are described, as well as the influence HIF has on cancer cell metabolism. HIF-1 activation has been related to angiogenesis, erythropoiesis and modulation of key enzymes involved in aerobic glycolysis, thereby modulating key processes required for the Warburg effect. In this review we discuss the molecular aspects of the Warburg effect with a particular emphasis on the role of the HIF-1 and the PI3K pathway.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is often cured with standard chemoimmunotherapy, but there is great heterogeneity in presentation and outcomes. METHODS: By using Surveillance, Epidemiology, and End Results (SEER) data from 13 registries across the United States, the authors examined differences in incidence and survival for DLBCL by race. International Classification of Diseases for Oncology, third edition histology codes 9678, 9679, 9680, and 9684 were used to identify cases. RESULTS: From 1992 to 2007, 38,522 cases of DLBCL were recorded in SEER. Sixty-five percent of black patients compared with 37% of white patients presented at age 60 years, 52% of blacks compared with 44% of whites presented with stage III/IV disease, and 31% of black versus 24% of white patients presented with B symptoms (all P < .001). Although survival improved by era of diagnosis for all races (log rank P < .001), 2-year relative survival rates were better for women than men (61% vs 58%, P < .001) and white than black patients (60% vs 50%, P < .001). Black race, male sex, age at diagnosis >60, advanced stage, and B symptoms at diagnosis were predictors of worse survival (P < .001). CONCLUSIONS: Black patients with DLBCL in the United States present at younger age, more advanced stage, and have inferior survival. Epidemiological studies that examine the biological variants of DLBCL in concert with race are needed to elucidate the etiology of these disparities.