Sherry A Bradford
Posters-Accepted Abstracts: Chemotherapy
Background: Chemotherapeutic treatment regimens tend to be deleterious and toxic to cancer patients. Thus, today many clinicians are changing their clinical practices opting for targeted and/or ancillary drug treatments that kill the tumor cell populations while sparing healthy cells. Greater than 70% of all cancer types rely on cytosolic aerobic glycolysis for energy production, an inefficient means of generating ATP rather than mitochondrial oxidative phosphorylation resulting in an acidic microenvironment conducive to their growth and proliferation. DCA inhibits Pyruvate Dehydrogenase Kinase (PDK) thereby increasing influx of pyruvate into the mitochondria, promoting glucose oxidation, reversing the suppressed mitochondria thus promoting apoptosis in cancer cells. Thus, it would be reasonable to propose that cancer cells would likely be sensitive DCA. Therefore, a prospective study of the efficacy of DCA as a potential chemotherapeutic agent was conducted. Results: 27 solid-tumors were studied; 3 of 27 exhibited high*/intermediate sensitivity to DCA as a single agent; 7 of 27 exhibited high*/intermediate sensitivity to DCA in combination with chemotherapeutic agent(s). 9 of 27 exhibited no sensitivity to DCA as a single agent or in combination. Clinical outcomes further validated the in vitro data. Conclusion: Our findings indicate a potential role for DCA in oncology therapeutics in a wide range of cancer types. Moreover, it is stimulating to propose that autophagy may be the focus rather than apoptosis since cancer cells circumvent this pathway and are sensitive to autophaghic communicants. Nonetheless, randomized controlled clinical trials must be designed to further correlate and validate this preliminary pilot study on DCA.