Frontiers in Clinical Drug Research - Anti-Cancer Agents

Author(s): Patrícia L. Abreu and Ana M. Urbano

DOI: 10.2174/9781681082899116030006

Targeting the Warburg Effect for Cancer Therapy: A Long and Winding Road

Pp: 271-324 (54)

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Abstract

SHS investigation development is considered from the geographical and historical viewpoint. 3 stages are described. Within Stage 1 the work was carried out in the Department of the Institute of Chemical Physics in Chernogolovka where the scientific discovery had been made. At Stage 2 the interest to SHS arose in different cities and towns of the former USSR. Within Stage 3 SHS entered the international scene. Now SHS processes and products are being studied in more than 50 countries.

Abstract

In the 1920s, Otto Warburg, one of the leading biochemists of the 20th century, uncovered a striking phenotype of cancer cells: their increased dependence on lactic acid fermentation for energy production compared to that of the normal cells from which they derived. Warburg viewed this metabolic particularity of cancer cells, which came to be known as the Warburg effect, as a driving force in carcinogenesis. This perception suggested a novel path for cancer therapy, a strategy that Warburg himself proposed and defended with passion to his death. However, for many decades, both his metabolic theory of cancer and suggested therapeutic approach were essentially ignored by cancer researchers, who were mostly focused on the genetic basis of the disease and on the intricacies of the pathways known to promote cellular proliferation, differentiation and death. Still, thanks to the combined efforts of those who chose to pursue Warburg’s line of research, experimental evidence supporting and extending Warburg´s findings on the metabolism of cancer cells accumulated. In the 1980s, 18F-deoxyglucose positron emission tomography (18FDG–PET) was implemented in the clinic. This metabolic imaging technique, which is based on the avidity of cancer cells for glucose, represents, to this day, the only successful exploitation of the Warburg effect for medical purposes. The wide success of 18FDG–PET in the diagnosis and staging of tumors is among the factors most responsible for renewing interest in the central carbon metabolism of cancer cells. This renewed interest was further boosted by the discovery of multiple links between central carbon metabolism and cellular proliferation, differentiation and death and culminated in the recent classification, by Weinberg and Hanahan, of tumor metabolism as an emerging cancer hallmark. Tremendous research effort is now being devoted into a more detailed and comprehensive elucidation of the metabolic rewiring that accompanies neoplastic transformation and, unsurprisingly, targeting the metabolic peculiarities of tumors has become a hot topic in drug discovery. This chapter summarizes past and current efforts at targeting the Warburg effect for selective cancer therapies.

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