TY - JOUR
T1 - Targeted approach to metastatic colorectal cancer
T2 - What comes beyond epidermal growth factor receptor antibodies and bevacizumab?
AU - Troiani, Teresa
AU - Martinelli, Erika
AU - Morgillo, Floriana
AU - Capasso, Anna
AU - Nappi, Anna
AU - Sforza, Vincenzo
AU - Ciardiello, Fortunato
PY - 2013/1
Y1 - 2013/1
N2 - The prognosis of patients with cancer remains poor in spite of the advances obtained in recent years with new therapeutic agents, new approaches in surgical procedures and new diagnostic methods. The discovery of a plethora of cellular targets and the rational generation of selective targeting agents has opened an era of new opportunities and extraordinary challenges. The specificity of these agents renders them capable of specifically targeting the inherent abnormalities of cancer cells, potentially resulting in less toxicity than traditional nonselective cytotoxics. Among the many new types of rationally designed agents are therapeutics targeting various strategic facets of growth signal transduction, malignant angiogenesis, survival, metastasis and cell-cycle regulation. The evaluation of these agents is likely to require some changes from the traditional drug development paradigms to realize their full potential. Inhibition of the epidermal growth factor receptor and the vascular endothelial growth factor have provided proof of principle that disruption of signal cascades in patients with colorectal cancer has therapeutic potential. This experience has also taught us that resistance to such rationally developed targeted therapeutic strategies is common. In this article, we review the role of signal transduction in colorectal cancer, introduce promising molecular targets, and outline therapeutic approaches under development.
AB - The prognosis of patients with cancer remains poor in spite of the advances obtained in recent years with new therapeutic agents, new approaches in surgical procedures and new diagnostic methods. The discovery of a plethora of cellular targets and the rational generation of selective targeting agents has opened an era of new opportunities and extraordinary challenges. The specificity of these agents renders them capable of specifically targeting the inherent abnormalities of cancer cells, potentially resulting in less toxicity than traditional nonselective cytotoxics. Among the many new types of rationally designed agents are therapeutics targeting various strategic facets of growth signal transduction, malignant angiogenesis, survival, metastasis and cell-cycle regulation. The evaluation of these agents is likely to require some changes from the traditional drug development paradigms to realize their full potential. Inhibition of the epidermal growth factor receptor and the vascular endothelial growth factor have provided proof of principle that disruption of signal cascades in patients with colorectal cancer has therapeutic potential. This experience has also taught us that resistance to such rationally developed targeted therapeutic strategies is common. In this article, we review the role of signal transduction in colorectal cancer, introduce promising molecular targets, and outline therapeutic approaches under development.
KW - Aurora kinase inhibitors
KW - Colorectal cancer
KW - Insulin-like growth factor receptor inhibitors
KW - MET inhibitors
KW - New therapies
KW - Src kinase inhibitors
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U2 - 10.1177/1758834012462462
DO - 10.1177/1758834012462462
M3 - Article
C2 - 23323147
AN - SCOPUS:84877898048
VL - 5
SP - 51
EP - 72
JO - Therapeutic Advances in Medical Oncology
JF - Therapeutic Advances in Medical Oncology
SN - 1758-8340
IS - 1
ER -