The soy compound genistein has been observed preclinically to inhibit bladder cancer growth with one potential mechanism being inhibition of epidermal growth factor receptor phosphorylation (p-EGFR).
A phase 2 randomized, placebo-controlled trial investigated whether daily, oral genistein (300 or 600 mg/day as the purified soy extract G-2535) for 14-21 days before surgery alters molecular pathways in bladder epithelial tissue in 59 subjects diagnosed with urothelial bladder cancer (median age 71). G-2535 treatment was well tolerated; observed toxicities were primarily mild to moderate gastrointestinal or metabolic and usually not attributed to study drug. Genistein was detected in plasma and urine of subjects receiving G-2535 at concentrations greater than placebo subjects' but were not dose-dependent. Reduction in bladder cancer tissue p-EGFR staining between the placebo arm and the combined genistein arms was significant at the protocol-specified significance level of 0.10 (p=0.07). This difference was most prominent when comparing the 300 mg group vs placebo (p=0.015), but there was no significant reduction in p-EGFR staining between the 600 mg group and placebo. No difference in normal bladder epithelium p-EGFR staining was observed between treatment groups. No significant differences in tumor tissue staining between treatment groups was observed for COX-2, Ki-67, activated caspase 3, Akt, p-Akt, MAPK, or p-MAPK. No significant differences in urinary Survivin or BLCA-4 levels between treatment groups were observed. Genistein displayed a possible bimodal effect (more effective at the lower dose) on bladder cancer tissue EGFR phosphorylation that should be evaluated further, possibly in combination with other agents.
Written by:
Messing E, Gee JR, Saltzstein DR, Kim K, Disant'agnese PA, Kolesar J, Harris L, Faerber A, Havighurst TC, Young JM, Efros M, Getzenberg RH, Wheeler MA, Tangrea J, Parnes HL, House M, Busby JE, Hohl RJ, Bailey HH. Are you the author?
Dept of Urology, Univ of Rochester Medical Center.
Reference: Cancer Prev Res (Phila). 2012 Jan 31. Epub ahead of print.
doi: 10.1158/1940-6207.CAPR-11-0455
PubMed Abstract
PMID: 22293631
