Role of novel targeted agents in the treatment of metastatic colorectal cancer

Abstract

Modern chemotherapy regimens, combining bolus or infused schedules of 5-fluorouracil (5-FU) with irinotecan or oxaliplatin, have significantly improved the treatment outcomes of patients with metastatic colorectal cancer (CRC). The addition of novel targeted agents to chemotherapy has the potential to increase the median survival of patients with metastatic CRC beyond 2 years. Bevacizumab, a monoclonal antibody (mAb) to vascular endothelial growth factor, has an established role in first-line treatment in combination with either 5-FU/leucovorin or irinotecan/5-FU/leucovorin regimens, while cetuximab, a mAb to epidermal growth factor receptor, in combination with irinotecan is more suitable for the treatment of refractory metastatic CRC. The use of bevacizumab in later stages of the disease and cetuximab in chemotherapynaive patients as well as concurrent treatment with both agents is still under investigation. The landmark studies leading to the approval of these agents in the treatment of metastatic CRC as well as associated toxicity profiles and detailed treatment recommendations are discussed in this review.

Telomerase- and angiogenesis-related gene responses to irradiation in human umbilical vein endothelial cells

“…Tumor angiogenesis involves a number of angiogenic factors, including vascular endothelial growth factor (VEGF), angiopoietin, basic fibroblast growth factor (FGF), and platelet-derived growth factor. VEGF exerts a variety of effects on vascular ECs that together promote the formation of new blood vessels, stimulate ECs to migrate and divide, and profoundly alter their pattern of gene expression (10,11). VEGF has been reported to delay the onset of senescence in microvascular ECs and to reverse the senescence process (12).…”

“…IR targets both tumors and ECs. The radiosensitivity of the tumor microvasculature and microvascular damage significantly contributes to tumor response to radiation (11). Thus, targeting an intrinsic treatment threshold in tumor vasculature ECs sensitizes the tumor cells to IR.…”

Predicting the response to targeted therapy in metastatic colorectal cancer

“…Colorectal cancer is the second most common cause of cancer‐related deaths in Australia 1 . While the 5‐year survival of metastatic colorectal cancer (mCRC) is less than 10%, 2 novel targeted therapies offer promise in improving patient outcomes.…”