Research conducted by leading cancer metabolism researchers at Stony Brook University, Paul M. Bingham and Zuzana Zachar, is showing promise in this approach with their clinical investigation of a new class of compounds that disrupt cancer cell mitochondrial metabolism.
The lead compound of a new chemical class with a novel mechanism, called CPI-613, attacks two key cancer cell building block targets in one shot to stop tumor growth.
Discoveries by Drs. Bingham, Zachar and colleagues at Stony Brook University led to a technology for the design of drugs that disrupt cancer metabolism.
In collaboration with Cornerstone Pharmaceuticals, they are evaluating the basic mechanisms of actions behind this class of agents.
In 2008, initial stage (phase I) Food and Drug Administration (FDA)-approved clinical trials of anti-cancer compounds began. As the exclusive licensee, Cornerstone is sponsoring the clinical trials, which have now moved into phase II.
The latest research findings in the paper highlights the results of cultured cell studies by the research team in support of the phase II clinical trials.
Bingham said that his team discovered that CPI-613 acts as a 'cocktail of one,' meaning the single agent kills cancer cells selectively by simultaneously attacking two crucial metabolic enzymes in cancer cells, and each by a different mechanism.
The critical clinical implication of this duel mechanism of action is that unlike other current anti-cancer agents, CPI-613 has the capacity to attack tumor metabolism more robustly than single-target agents and be less vulnerable to evolved drug resistance, Bingham said.
Dr. Bingham added that CPI-613's two-pronged attack on this cancer cell cycle efficiently and selectively induces cancer cell death in a variety of cancers, including solid tumors and also in leukemia and lymphoma.
The agent attacks and deactivates two lipoate-using enzymes that are major entry points for energy and carbon into the mitochondrial citric acid cycle of the cancer cell.
The study is published in Cancer and Metabolism.