The Dichotomous Role of the Glycolytic Metabolism Pathway in Cancer Metastasis: Interplay with the Complex Tumor Microenvironment and Novel Therapeutic Strategies

Publication date: Available online 21 August 2019Source: Seminars in Cancer BiologyAuthor(s): Btissame El Hassouni, Carlotta Granchi, Andrea Vallés-Martí, I Gede Putu Supadmanaba, Giulia Bononi, Tiziano Tuccinardi, Niccola Funel, Connie R. Jimenez, Godefridus J. Peters, Elisa Giovannetti, Filippo MinutoloAbstractCancer metastasis to distant organs is initiated by tumor cells that disseminate from primary heterogeneous tumors. The subsequent growth and survival of tumor metastases depend on different metabolic changes, which constitute one of the enigmatic properties of tumor cells. Aerobic glycolysis, ‘the Warburg effect’, contributes to tumor energy supply, by oxidizing glucose in a faster manner compared to oxidative phosphorylation, leading to an increased lactate production by lactate dehydrogenase A (LDH-A), which in turn affects the immune response. Surrounding stromal cells contribute to feedback mechanisms further prompting the acquisition of pro-invasive metabolic features. Hence, therapeutic strategies targeting the glycolytic pathway are intensively investigated, with a special interest on their anti-metastatic properties. Various small molecules, such as LDH-A inhibitors, have shown pre-clinical activity against different cancer types, and blocking LDH-A could also help in designing future complimentary therapies. Modulation of specific targets in cells with an altered glycolytic metabolism should indeed result in a milder and distinct toxicity profile, comp...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research