Abstract
Despite being one of the most frequently diagnosed cancers worldwide, prognosis of metastatic colorectal cancer (CRC) was poor. Development and introduction of biologic agents in treatment of patients with metastatic CRC have brought improved outcomes. Monoclonal antibodies directing epidermal growth factor receptors and vascular endothelial growth factor are main biologic agents currently used in treatment of metastatic CRC. Encouraged by results from many clinical trials demonstrating efficacy of those monoclonal antibodies, the combination therapy with those targeted agents and conventional chemotherapeutic agents has been established as the standard therapy for patients with metastatic CRC. However, emergency of resistance to those target agents has limited the efficacy of treatment, and strategies to overcome the resistance are now being investigated by newly developed biological techniques clarifying how to acquire resistance. Here, we introduce mechanisms of action of the biologic agents currently used for treatment of metastatic CRC and several landmark historical clinical studies which have changed the main stream of treatment. The mechanism of resistance to those agents, one of serious problems in treatment metastatic CRC, and ongoing clinical trials to overcome the limitations and improve treatment outcomes will also be presented in this review.
Highlights
Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer and the third leading cause of disease mortality in the United States [1]
Introduction of monoclonal antibodies, such as antiepidermal growth factor receptor (EGFR) antibody or antivascular endothelial growth factor (VEGF) antibody, in combination with the chemotherapeutic agents in treatment of metastatic CRC have brought improvement of survival, and recent clinical trials performed with those monoclonal antibodies at first-line treatment showed median survival of 17.9 to 29.9 months [5,6,7]
Enormous progress has been made in treatment of metastatic CRC, the prognosis still remains poor
Summary
Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer and the third leading cause of disease mortality in the United States [1]. Introduction of monoclonal antibodies, such as antiepidermal growth factor receptor (EGFR) antibody or antivascular endothelial growth factor (VEGF) antibody, in combination with the chemotherapeutic agents in treatment of metastatic CRC have brought improvement of survival, and recent clinical trials performed with those monoclonal antibodies at first-line treatment showed median survival of 17.9 to 29.9 months [5,6,7]. Encouraged by these results, anti-EGFR or anti-VEGF antibodies are recommended as the standard therapy of first-line chemotherapy in treatment of metastatic CRC. This review is focused on targeted therapies applicable to patients with unresectable metastatic CRC, mechanisms of action of the biologic agents, and limitations of the targeted therapies and solutions
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