Preliminary Findings on the Use of Targeted Therapy in Combination with Sodium Phenylbutyrate in Colorectal Cancer after Failure of Second-Line Therapy—A Potential Strategy for Improved Survival

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer death related mortality with 1.2 million new cases diagnosed annually worldwide. Despite remarkable advances in the treatment of resectable CRC, advanced disease that recurs following initial two lines of chemotherapy, remains incurable. Targeted therapies using a single agent or in combination with other drugs have been tested in a number of clinical trials, with only moderate improvement. Here we present preliminary findings of improved overall survival (OS) using a combination of sodium phenylbutyrate with various targeted and chemotherapeutic agents in stage IV CRC patients who had failed at least two lines of chemotherapy. Results suggest a strategy of simultaneous interruption of signal transduction involving EGFR (VEGF) KRAS-ERK and PI3K-AKT pathways and interference with cell cycle, cancer cell metabolism, maintenance of cancerous stem cells, and promotion of apoptosis. In a group of 15 patients, median OS was higher compared to other third-line therapies (14.7 months compared to between 4.8 and 9.5 months in other studies). Given the understanding that our findings are preliminary, we propose the validation of our initial results using a well-designed phase I/II trial in recurrent advanced colorectal cancer.

Procaine Induces Epigenetic Changes in HCT116 Colon Cancer Cells

“…When combined with sodium phenylbutyrate, procaine in both concentrations exhibited an ability to significantly reduce the cell count which was lower than using procaine solely. This might highlight the antagonistic effect of sodium phenylbutyrate when combined with procaine, in which the former drug inhibited procaine from performing its action [28–31]. …”