Mitochondrial metabolism as a pharmacological target for cancer therapeutics

Mitochondria are essential cellular organelles that were first identified in the mid-19th century. Despite more than 150 years of research and the accumulation of vast wealth of knowledge on mitochondrial structure and functions, new breakthroughs are still being made in recent years in key areas of mitochondrial biology. In the field of cancer research, major progress includes the elucidation of the role of mitochondria in cancer metabolic reprogramming, the discovery of signaling pathways in the crosstalk between mitochondria and the nucleus, the revelation of significant mitochondrial impact on tumor microenvironment and immune cells, the realization of the intriguing interplay between gut microbiota and cancer metabolism, the identification of molecular targets in mitochondria and the related pathways, and the development of mitochondria-targeted drugs such as mitocans for cancer treatment. This new progress underscores the essential role of mitochondria as multifaceted regulators of cancer metabolism, signal transduction, and cell survival, and as key pharmacological targets. This article will provide an up-to-date review of these important areas. The implications of these new research advances in cancer pharmacology and therapeutics will be explored, and interesting concepts that provide alternative theories for bioenergetics will also be discussed. SIGNIFICANCE STATEMENT: As a central hub for cellular energy production and biomolecule metabolism, mitochondria play essential roles in regulating metabolic and redox homeostasis, significantly affecting cell proliferation, survival, and sensitivity to pharmacological agents. Dysfunction of mitochondria in cancer cells alters these vital processes and affects tumor growth and therapeutic responses. Thus, a comprehensive understanding of mitochondrial alterations, the underlying regulatory mechanisms, and their impacts on pharmacological targets is pivotal for developing more effective therapeutic agents with significant clinical implications in cancer treatment.