Opportunities and challenges of integrating HIF-1 into clinical practice for cancer treatment

Abstract

The Warburg effect is one of the most studied mechanisms involved in cancer progression. It refers to the increased glucose uptake by cancer cells through aerobic glycolysis, instead of the Krebs cycle that takes place under normal conditions, followed by lactic acid fermentation. This mechanism is regulated by hypoxia-inducible factor-1 (HIF-1), a transcription factor that regulates the expression of genes responsible for the synthesis of proteins involved in glucose metabolism. Overexpression of HIF-1 has been linked to the Warburg effect. While several HIF-1-targeted strategies have been investigated, the majority have proven to be unsuccessful, especially in cases of aggressive tumors with hypoxic tumor microenvironments. Current strategies expand beyond conventional chemotherapeutic agents and include chemodynamic therapy, radiation therapy, and immune checkpoint molecules. The aim of this literature review is to highlight the implication of HIF-1 in the Warburg effect and the limitations that render cancer treatment less effective.