Development of ZD1839 in colorectal cancer.
Colorectal cancer is one of the most frequent human malignancies. Therapeutic options are mainly limited to chemotherapy with 5-fluorouracil in various schedules or in combination with irinotecan and oxaliplatin; however, novel approaches are also in development. These new agents specifically attack molecular targets involved in tumor biology. One such target is the epidermal growth factor receptor (EGFR), which is highly expressed in many tumors and is associated with a poor prognosis. The EGFR plays a key role in cell proliferation and has been implicated in several processes that mediate cancer progression. ZD1839 is an orally active, selective EGFR tyrosine kinase inhibitor that has shown extensive preclinical activity and favorable tolerability in advanced clinical trials in a variety of tumors. In colorectal cancer cells, ZD1839 has shown both in vitro and in vivo antitumor activity as monotherapy or in combination with cytotoxic agents such as paclitaxel and irinotecan. Preclinical data have also shown that ZD1839 reverses resistance to irinotecan and enhances its efficacy by improving oral bioavailability. These studies indicate that EGFR inhibition by ZD1839 may have a valuable role in the treatment of colorectal cancer, and clinical studies in patients with colorectal cancer are ongoing.
Douglass
Edwin C
EC
AstraZeneca Pharmaceuticals, LP, Wilmington, DE 19850, USA.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors*; D000077156:Gefitinib; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D011799:Quinazolines; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib