Targeting metabolic pathways for head and neck cancers therapeutics

• Published in: Cancer and metastasis reviews Vol. 36; no. 3; pp. 503 - 514
• Main Authors: Yamamoto, Masashi, Inohara, Hidenori, Nakagawa, Takashi
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2017; Springer; Springer Nature B.V
• Subjects: Anaerobic conditions; Animals; Antimetabolites, Antineoplastic - pharmacology; Antimetabolites, Antineoplastic - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Cell division; Dehydrogenase; Dehydrogenases; Development and progression; Energy metabolism; Enzymes; Genes; Genetic transcription; Genetic transformation; Glucose metabolism; Glycolysis; Head & neck cancer; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - metabolism; Homeopathy; Humans; Hypoxia; Isocitrate dehydrogenase; Materia medica and therapeutics; Metabolic Networks and Pathways - drug effects; Metabolic pathways; Metabolism; Molecular modelling; Molecular Targeted Therapy; Oncology; Pathogenesis; Physiological aspects; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Succinate dehydrogenase; Therapeutics; Transcription factors; Tumor suppressor genes; Glycolysis; Oxidative phosphorylation; TCA cycle; NAD biosynthesis; Head and neck squamous cell carcinoma (HNSCC); Warburg effect
• ISSN: 0167-7659; 1573-7233
• DOI: 10.1007/s10555-017-9691-z

Cancer cells have distinctive energy metabolism pathways that support their rapid cell division. The preference for anaerobic glycolysis under the normal oxygen condition is known as the Warburg effect and has been observed in head and neck cancers. These metabolic changes are controlled by cancer-related transcription factors, such as tumor suppressor gene and hypoxia inducible factor 1α. In addition, various metabolic enzymes also actively regulate cancer-specific metabolism including the switch between aerobic and anaerobic glycolysis. For a long time, these metabolic changes in cancer cells have been considered a consequence of transformation required to maintain the high rate of tumor cell replication. However, recent studies indicate that alteration of metabolism is sufficient to initiate tumor transformation. Indeed, oncogenic mutations in the metabolic enzymes, isocitrate dehydrogenase and succinate dehydrogenase, have been increasingly found in various cancers, including head and neck cancers. In the present review, we introduce recent findings regarding the cancer metabolism, including the molecular mechanisms of how they affect cancer pathogenesis and maintenance. We also discuss the current and future perspectives on therapeutics that target metabolic pathways, with an emphasis on head and neck cancer.