Cancer Metabolism Historical Perspectives: A Chronicle of Controversies and Consensus

A century ago, Otto Warburg’s work sparked the field of cancer metabolism, which has since taken a tortuous path. As evidence accumulated over the decades, consensus views of causes of cancer emerged, whereby genetic and epigenetic oncogenic drivers promoted immune evasion and induced new blood vessels and neoplastic metabolism to support tumor growth. Neoplastic cells abandon social cues of intercellular cooperation, escape tissue confinement, metastasize, and ultimately kill the host. Herein, key milestones in the study of cancer metabolism are chronicled with an emphasis on carbohydrate metabolism. The field began with a cancer cell–autonomous view that has been refined by a richer understanding of solid cancers as growing, immune-suppressive, complex organs comprising different cell types that are nourished by a variety of nutrients and variable amounts of oxygen through abnormal neovasculatures. Based on foundational historical studies, our current understanding of cancer metabolism offers a hopeful outlook for targeting metabolism to enhance cancer therapy.