[Molecular targeted therapy in colorectal cancer and its resistance].
The prognosis of advanced colorectal cancer has been improved by introduction of molecular targeting agents, such as bevacizumab and cetuximab. Several clinical trials revealed a median survival time of more than 2 years. However, the main purpose of chemotherapy for advanced colorectal cancer has not been cure but prolongation of life to date. One explanation of the difficulty of cure is the inherent and/or acquired resistance to chemotherapeutic agents and molecular targeting agents. A better understanding of the mechanisms of inherent resistance will make it possible to identify predictive markers of responder or non-responder to select the optimal patients for a certain drug. Additionally, knowledge of the acquired mechanism will provide for the rational development of therapies that circumvent or overcome resistance. Although the mechanisms of the resistance of molecular targeting agents for colorectal cancer are still unclear, the inherent resistance to cetuximab or panitumumab by why of expression of KRAS mutation is the first breakthrough in this field. Further basic research and biomarker analysis of large clinical study are necessary to clarify the resistance to molecular targeting agents.
Shitara
Kohei
K
Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
Muro
Kei
K
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use*; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000276:immunology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D066246:ErbB Receptors; D015689:Oncogene Protein p21(ras)