In a study published in Frontiers in Oncology, MCW Cancer Center scientists synthesized mitochondria-targeted molecules to potently and selectively inhibit cancer cell proliferation and growth. Their discoveries may lead to novel targeted drugs for use in cancer treatment alone or in combination with other therapies.
A mitochondrion is the cellular powerhouse generating energy-rich molecules like adenosine triphosphate (ATP). Normal cells produce ATP from oxygen metabolism in mitochondria. However, cancer cells use a process called glycolysis (i.e., the fermentation of sugar) to produce ATP.
“For a long time, it was thought that the main reason why cancer cells use sugar rather than oxygen for energy is that cancer cells don’t have functional mitochondria,” said first author Balaraman Kalyanaraman, PhD, professor, Biophysics. “Our group and others proved that this long-held belief is not true.”
By developing and testing this novel class of mitochondria-targeted molecules in cancer cells and in preclinical animal models, and understanding the pharmacokinetics and pharmacodynamics of these molecules, the study team hopes to obtain an investigational new drug status from the FDA and initiate clinical trials targeting mitochondrial metabolism that include patients with diverse racial and ethnic backgrounds.
Recent publications suggest that race and ethnicity are factors affecting mitochondrial metabolism in cancer cells, and that mitochondrial metabolism in white cancer patients is remarkably different than in patients from other racial and ethnic groups. “In Black patients with bladder cancer, the mitochondrial metabolism is considerably higher. This differential mitochondrial metabolism provides a compelling rationale for testing mitochondria-targeted drugs in Black patients with bladder cancer,” said Dr. Kalyanaraman.
With support of the National Cancer Institute (NCI), the team is testing the preclinical efficacy of a mitochondria-targeted drug in different mice models of lung cancer. Dr. Kalyanaraman noted that they have a U.S. patent for the use of this molecule to treat several types of cancers. “We hope that, after completion of this contract, the NCI will test the efficacy and toxicology of this drug in larger animals,” he said.