| Title | Effective Treatment of Advanced Colorectal Cancer by Rapamycin and 5-FU/Oxaliplatin Monitored by TIMP-1. | | Author(s) | Wagner M, Roh V, Strehlen M, Laemmle A, Stroka D, Egger B, Trochsler M, Hunt KK, Candinas D, Vorburger SA | | Institution | Department of Visceral and Transplantation Surgery and Department of Clinical Research, Inselspital, University Hospital Bern and University of Bern, CH-3010, Bern, Switzerland. | | Source | J Gastrointest Surg 2009 Jun 30. | | Abstract | AIM: The mTOR-inhibitor rapamycin has shown antitumor activity in various tumors. Bedside observations have suggested that rapamycin may be effective as a treatment for colorectal carcinomatosis.
METHODS: We established an orthotopic syngenic model by transplanting CT26 peritoneal tumors in Balb/C mice and an orthotopic xenograft model by transplanting SW620 peritoneal tumors in nu/nu mice. Expression levels of tissue inhibitor of matrix-metalloproteinases 1 (TIMP-1) in the tumor and serum was determined by enzyme-linked immunosorbent assay.
RESULTS: Rapamycin significantly suppressed growth of syngenic and xenografted peritoneal tumors. The effect was similar with intraperitoneal or oral rapamycin administration. Tumor suppression was further enhanced when rapamycin was combined with 5-fluorouracil and/or oxaliplatin. The combination treatment showed no acute toxicity. TIMP-1 serum levels correlated well (CC = 0.75; P < 0.01) with rapamycin treatment.
CONCLUSIONS: Rapamycin suppressed advanced stage colorectal cancer, even with oral administration. Combining rapamycin with current chemotherapy regimens significantly increased antitumor efficacy without apparent toxicity. The treatment efficacy correlated with serum TIMP-1 levels, suggesting its potential as a surrogate marker in future clinical trials. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19565301 |
|
