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Numerous preclinical studies have shown efficacy of oncolytic adenoviruses for treatment of several tumor types, 3 including colorectal cancer. Even though early detection and prevention strategies have a key role in improving colorectal cancer statistics, also new therapeutic options are needed. 1, 2 Metastatic colorectal cancer, being the most aggressive form of the disease, can be cured only rarely. Incidence rates have increased during past decades, whereas 5-year survival rates have improved but remain between 60 and 40% in different countries. Co-administration of MME and oncolytic adenovirus may be a suitable approach for further optimization aiming at clinical applications for metastatic colorectal cancer.Ĭolorectal cancer is the fourth most common type of cancer in men and the third most common in women worldwide, with over one million new patients diagnosed each year. This study demonstrates for the first time in a metastatic animal model that MME, as a monotherapy or in combination with oncolytic virus, does not increase tumor invasiveness. Contradictory results of effects of MME on tumorigenesis and metastasis formation have been reported in the literature. Combination therapy showed no increased mortality in comparison with either monotherapy alone.
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In a liver metastatic colorectal cancer model, intra-tumoral treatment of primary tumors from HT29 cells with MME monotherapy or with oncolytic adenovirus inhibited tumor growth. MME improved the overall antitumor efficacy of oncolytic adenovirus in subcutaneous HCT116 xenografts. In this study, the ECM-degrading proteases relaxin, hyaluronidase, elastase and macrophage metalloelastase (MME) were tested for their antitumor efficacy alone and in combination with oncolytic adenovirus. As oncolytic viruses kill preferentially cancer cells, high extracellular matrix (ECM) content constitutes potential barriers for viral penetration within tumors. Poor spreading of the virus through tumor tissue is one of the major issues limiting efficacy. However, clinical trials have demonstrated that single-agent therapy in advanced tumor masses is rarely curative. Oncolytic adenoviruses are a promising treatment alternative for many advanced cancers, including colorectal cancer.