Improving gemcitabine-mediated radiosensitization using molecularly targeted therapy: a review.
In the last three decades, gemcitabine has progressed from the status of a laboratory cytotoxic drug to a standard clinical chemotherapeutic agent and a potent radiation sensitizer. In an effort to improve the efficacy of gemcitabine, additional chemotherapeutic agents have been combined with gemcitabine (both with and without radiation) but with toxicity proving to be a major limitation. Therefore, the integration of molecularly targeted agents, which potentially produce less toxicity than standard chemotherapy, with gemcitabine radiation is a promising strategy for improving chemoradiation. Two of the most promising targets, described in this review, for improving the efficacy of gemcitabine radiation are epidermal growth factor receptor and checkpoint kinase 1.
Morgan
Meredith A
MA
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109-5637, USA. mmccrack@med.umich.edu
Parsels
Leslie A
LA
Maybaum
Jonathan
J
Lawrence
Theodore S
TS
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000071877:Checkpoint Kinase 1; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011494:Protein Kinases; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D000093542:Gemcitabine
D047428:Protein Kinase Inhibitors; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D011494:Protein Kinases; D066246:ErbB Receptors; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D000093542:Gemcitabine