Anti-angiogenic agents in metastatic colorectal cancer

Abstract

Colorectal cancer (CRC) is a major public health concern being the third leading cause of cancer mortality in the United States. The availability of better therapeutic options has led to a decline in cancer mortality in these patients. Surgical resection should be considered in all stages of the disease. The use of conversion therapy has made surgery a potentially curative option even in patients with initially unresectable metastatic disease. In this review we discuss the role of various antiangiogenic agents in patients with metastatic CRC (mCRC). We describe the mechanism of action of these agents, and the rationale for their use in combination with chemotherapy. We also review important clinical studies that have evaluated the safety and efficacy of these agents in mCRC patients. Despite the discovery of several promising anti-angiogenic agents, mCRC remains an incurable disease with a median overall survival of just over 2 years in patients exposed to all available treatment regimens. Further insights into tumor biology and tumor microenvironment may help improve outcomes in these patients. Core tip: Colorectal cancer is a major health concern and a leading cause of cancer mortality worldwide. New innovations have provided improved survival in recent years. In this review, we outline the novel anti-angiogenic agents and their respective roles in metastatic colorectal cancer. In addition to three agents approved by the Food and Drug Administration, several alternative anti-angiogenic agents hold promise for use in the metastatic setting.Konda B, Shum H, Rajdev L. Anti-angiogenic agents in metastatic colorectal cancer. World J Gastrointest Oncol 2015; 7(7): 71-86 Available from:

MicroRNA-203-mediated posttranscriptional deregulation of CPEB4 contributes to colorectal cancer progression

“…Nearly one-fifth of colorectal cancer patients are diagnosed at an advanced metastatic stage and more than 50% will ultimately develop metastases [2]. Even with aggressive intervention (including surgery, radiotherapy and chemotherapy), the survival rate of metastatic CRC patients remains poor [3]. To improve the prognosis of patients with malignant CRC, it is urgent to identify new molecular biomarkers that regulate malignant biological behavior of CRC cells and predict prognosis of CRC patients.…”

Comparative Effectiveness and Safety of Monoclonal Antibodies (Bevacizumab, Cetuximab, and Panitumumab) in Combination with Chemotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

“…The MoAbs used to treat patients with mCRC include cetuximab (CETUX) and panitumumab (PANIT) [5, 14], which act on the epidermal growth factor receptor (EGFR), and bevacizumab (BEVA) [5], which acts on the vascular endothelial growth factor (VEGF) [5, 24]. They have all improved progression-free survival (PFS) in patients with mCRC; however, there have been concerns expressed regarding the extent of their effectiveness with improving OS [14] and their cost-effectiveness [25, 26].…”

Targeting angiogenesis in gastrointestinal tumors: current challenges

“…As in normal adult tissues, tumor cells maintain a balance between the pro-angiogenic and the anti-angiogenic growth factors. But in some tumor cells, the balance is lost and the pro-angiogenic properties take over stimulating endothelial proliferation, neovascularization leading to tumor growth and metastases (3,4). Hence, inhibiting tumor angiogenesis has become a target for treatment of cancers.…”