Modulating Glycolysis to Improve Cancer Therapy

Cancer cells undergo metabolic reprogramming and switch to a 'glycolysis-dominant' metabolic profile to promote their survival and meet their requirements for energy and macromolecules. This phenomenon, also known as the 'Warburg effect,' provides a survival advantage to the cancer cells and make the tumor environment more pro-cancerous. Additionally, the increased glycolytic dependence also promotes chemo/radio resistance. A similar switch to a glycolytic metabolic profile is also shown by the immune cells in the tumor microenvironment, inducing a competition between the cancer cells and the tumor-infiltrating cells over nutrients. Several recent studies have shown that targeting the enhanced glycolysis in cancer cells is a promising strategy to make them more susceptible to treatment with other conventional treatment modalities, including chemotherapy, radiotherapy, hormonal therapy, immunotherapy, and photodynamic therapy. Although several targeting strategies have been developed and several of them are in different stages of pre-clinical and clinical evaluation, there is still a lack of effective strategies to specifically target cancer cell glycolysis to improve treatment efficacy. Herein, we have reviewed our current understanding of the role of metabolic reprogramming in cancer cells and how targeting this phenomenon could be a potential strategy to improve the efficacy of conventional cancer therapy.

Automated summary

Cancer cells undergo metabolic reprogramming to adopt a glycolysis-dominant metabolic profile, providing them with a survival advantage and contributing to a pro-cancerous tumor environment. This metabolic switch also leads to increased resistance to chemotherapy and radiation. Immune cells in the tumor microenvironment also exhibit a similar metabolic shift, leading to competition with cancer cells for nutrients. Targeting enhanced glycolysis in cancer cells has shown promise in improving treatment efficacy, but effective strategies are still lacking. This review highlights the importance of metabolic reprogramming in cancer cells and the potential of targeting it to enhance conventional cancer therapy.