TITLE:
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
AUTHORS:
Stanislaw R. Burzynski, Tomasz J. Janicki, Gregory S. Burzynski, Sheldon Brookman
KEYWORDS:
Colorectal Cancer, Colorectal Cancer Survival, Personalized Targeted Agents, Sodium Phenylbutyrate
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.13,
November
20,
2014
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.