Abstract
The usefulness of local collagenase in therapeutic approaches to solid tumors has been tested recently. In this study, we evaluate the safety and efficacy of intraperitoneal collagenase associated or not to mitomycin for treatment of colorectal peritoneal metastases in an experimental rat model. Using a fixed-dose procedure, we found that a dose of collagenase of 37 IU/mL administered for 15 min with a hyperthermia pump at 37.5 °C, both in isolation or associated to sequential treatment with intraperitoneal mitomycin, led to a macroscopic decrease in tumor volume as evaluated by the modified peritoneal cancer index (mPCI). Concerning the safety of the procedure, the animals showed no physiological or behavioral disorders during 8 weeks of follow-up. Local treatment for peritoneal metastases of colorectal origin with intraperitoneal collagenase has proved safe and effective in an experimental murine model. Therefore, the stroma-first approach by enzymatic breakdown of collagen from the tumor's extracellular matrix provides a new therapeutic target for colorectal peritoneal metastases.
Highlights
The usefulness of local collagenase in therapeutic approaches to solid tumors has been tested recently
When designing an appropriate experimental model of colorectal peritoneal carcinomatosis, we chose our previous model consisting of BD-IX syngeneic rats and the cell line DH/K-129
The peritoneal carcinomatosis rate achieved with our model was 80%, according to previous experiences
Summary
The usefulness of local collagenase in therapeutic approaches to solid tumors has been tested recently. We evaluate the safety and efficacy of intraperitoneal collagenase associated or not to mitomycin for treatment of colorectal peritoneal metastases in an experimental rat model. The stroma-first approach by enzymatic breakdown of collagen from the tumor’s extracellular matrix provides a new therapeutic target for colorectal peritoneal metastases. The components of the tumor microenvironment are related to drug resistance in several tumors One such component, the tumor stroma, protects against the arrival of therapeutic agents to target cancer cells[1]. The tumor stroma, protects against the arrival of therapeutic agents to target cancer cells[1] This microenvironment may be modified by reshaping the extracellular matrix (composed mainly of collagen fibers), thereby facilitating the penetration and delivery of drugs into tumors. Validated for clinical use in cancer, in vivo studies using intratumoral or intravenous routes to deliver collagenase have been carried out in murine tumor models
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