Targeted Therapy in Colorectal Cancer: Current Status and Future Challenges

Abstract

Treatment of metastatic colorectal cancer (mCRC) has progressed significantly over the last years, particularly with the introduction of targeted therapies. Two groups of agents targeting either the epidermal growth factor receptor (EGFR) or the vascular endothelial growth factor (VEGF) have been integrated into clinical practice. Currently available agents with established role include the anti-EGFR monoclonal antibodies (mAbs) cetuximab / panitumumab and the anti-VEGF mAb bevacizumab. This review presents an update on the clinical studies evaluating the role of anti-EGFR and anti-VEGF agents in mCRC. Moreover, we provide current data regarding the mechanism of action and pathways mediating resistance to these agents. In addition, we present recent data with respect to biomarkers and we discuss future therapeutic strategies.

The Addition of Target Therapy to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: A Review

“…It is a transmembrane glycoprotein containing an extracellular ligand-binding domain, a transmembrane region and an intracellular tyrosine-kinase domain with a regulatory carboxyl terminal segment [5]. …”

“…Its main pro over cetuximab is the reduced risk of allergic reactions. In fact, it is reported to have a lower incidence of infusion hypersensitivity reactions than cetuximab (1 vs. 3%) [5]. As with cetuximab, adverse events are dose related.…”

“…Bevacizumab vascular effects have been demonstrated in LARC patients [5]. Preclinical studies suggested that bevacizumab inhibits the growth of human xenograft tumors and decreases liver metastatic growth [32].…”

“…In light of these discouraging distant metastasis data, the development of alternative strategies for LARC has become a priority. Nowadays, based on the efficacy demonstrated in metastatic colorectal cancer, there is a growing interest in the addition of biological agents into standard neoadjuvant treatment of patients with LARC [5,6]. The biological agents that target the epidermal growth factor receptor (EGFR) or the vascular endothelial growth factor (VEGF) have been tested in the neoadjuvant setting due to their ability to specifically target cell signaling pathways involved in DNA repair, cell proliferation, apoptosis, and angiogenesis [6].…”

Pharmacogenetics and Pharmacogenomics of Colorectal Cancer: Moving Towards Personalized Medicine

“…Until the 80's, 5-fluorouracil (5-FU) was the only available drug to treat patients, with limited efficacy. Today, 4 cytotoxic agents (5-FU associated with folinic acid, capecitabine, oxaliplatin, irinotecan) and three monoclonal antibodies (cetuximab, panitumumab, bevacizumab) are available, mostly as part of combinations (Koutras et al, 2011). In particular, the rise of targeted therapies in digestive oncology has fueled a new hope by significantly stretching the therapeutic options available so far.…”