AACR 2023: Mechanistic Support for Using CPI-613 in Combination Therapy for Liver Cancer

By: Joshua D. Madera, MS
Posted: Friday, May 5, 2023

Investigative efforts aimed at assessing the efficacy of the lipoic acid analog CPI-613 in the treatment of cholangiocarcinoma have revealed its benefit when combined with other therapeutic agents, according to a presentation given at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract 2236/13). These findings should now be translated into clinical studies to determine the beneficial extent of this combination therapy for patients with cholangiocarcinoma, suggested Deepak Nagrath, PhD, of the University of Michigan, Ann Arbor, and colleagues.

Cholangiocarcinoma cell lines were obtained and either treated with the standard-of-care regimen of cisplatin and gemcitabine chemotherapy alone, CPI-613 alone, or a combination of the two aforementioned therapies. Cell lines treated with CPI-613 received a single dose of therapy or multiple smaller doses equivalent to the single dose. Plasma samples were obtained from patients at baseline, during, and after treatment for global metabolomic analysis. In addition, CPI-613 was combined with the IDH1 inhibitor ivosidenib to determine the combined effect of this regimen on anticancer activity.

The study findings revealed a synergistic effect of treatment when CPI-613 was combined with the standard-of-care chemotherapy regimen. When this regimen was dosed fractionally, the rate of oxygen consumption by mitochondria was reduced, which supports the use of extended rates of infusion in clinical practice. Furthermore, global metabolomic analyses showed specific genetic alterations in patients who achieved a complete response to therapy. These findings should be used to direct future studies aimed at identifying biomarkers of disease or treatment targets, according to the investigators. Moreover, combination therapy with ivosidenib and CPI-613 demonstrated a synergistic effect and may improve anticancer activity.

Disclosure: For full disclosures of the study authors, visit abstractsonline.com.

AACR Annual Meeting 2023

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