4.6 Review

Pieces of the Complex Puzzle of Cancer Cell Energy Metabolism : An Overview of Energy Metabolism and Alternatives For Targeted Cancer Therapy

Journal

CURRENT MEDICINAL CHEMISTRY
Volume 28, Issue 18, Pages 3514-3534

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929867327999200819123357

Keywords

Carbohydrate metabolism; lipid metabolism; amino acid metabolism; oncogenes and tumor suppressors; targeted therapy; alternative therapy

Funding

  1. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [88882.331359/2019-01, 88882.331336/2019-01]
  2. Conselho Nacional de Pesquisas e Desenvolvimento Tecnologico (CNPq) [313783/2018-7]
  3. Fundacao Carlos Chagas de Amparo a Pesquisa do Rio de Janeiro (FAPERJ) [E26/010.002670/2014]

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Cancer cell energy metabolism is focused on bioenergetic and biosynthetic pathways to meet the requirements of rapid proliferation, potentially influenced by genetic reprogramming. Enzymes crucial for cellular energy are targets of oncogenes and tumor suppressor proteins, with new therapeutic strategies aiming to disrupt cancer cell metabolism and genetic reprogramming.
Over the past decades, several advances in cancer cell biology have led to relevant details about a phenomenon called the 'Warburg effect'. Currently, it has been accepted that the Warburg effect is not compatible with all cancer cells, and thus the process of aerobic gly-colysis is now challenged by the knowledge of a large number of cells presenting mitochon-drial function. The energy metabolism of cancer cells is focused on the bioenergetic and bio-synthetic pathways in order to meet the requirements of rapid proliferation. Changes in the metabolism of carbohydrates, amino acids and lipids have already been reported for cancer cells and this might play an important role in cancer progression. To the best of our knowl-edge, these changes are mainly attributed to genetic reprogramming which leads to the trans-formation of a healthy into a cancerous cell. Indeed, several enzymes that are highly relevant for cellular energy are targets of oncogenes (e.g. PI3K, HIF1, and Myc) and tumor suppressor proteins (e.g. p53). As a consequence of extensive studies on cancer cell metabolism, some new therapeutic strategies have appeared that aim to interrupt the aberrant metabolism, in ad-dition to influencing genetic reprogramming in cancer cells. In this review, we present an overview of cancer cell metabolism (carbohydrate, amino acid, and lipid), and also describe oncogenes and tumor suppressors that directly affect the metabolism. We also discuss some of the potential therapeutic candidates which have been designed to target and disrupt the main driving forces associated with cancer cell metabolism and proliferation.

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