Drug resistance in colon cancer.
A significant obstacle for the successful management of patients with colorectal cancer is intrinsic drug resistance or, in patients who respond to chemotherapy, acquired drug resistance. Drug resistance can occur through a variety of mechanisms, including alterations in drug influx, drug efflux, intracellular metabolic activation, and intracellular catabolism, or through alterations in the drug's target. In addition, alterations in genes involved in the regulation of the cell cycle or in DNA damage repair may result in a cell becoming resistant to chemotherapy. In this chapter, the mechanisms of action and the mechanisms of resistance to the fluoropyrimidines and raltitrexed (Tomudex; Zeneca Pharmaceuticals, Wilmington, DE) are reviewed, focusing on newer studies using gastric and colorectal tumor samples obtained from patients. Clinical trials using this new information are anticipated.
Gorlick
R
R
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Bertino
J R
JR
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D002453:Cell Cycle; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use; D005493:Folic Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D015870:Gene Expression; D006801:Humans; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D013876:Thiophenes / Q000494:pharmacology* / Q000627:therapeutic use; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*
D000964:Antimetabolites, Antineoplastic; D004791:Enzyme Inhibitors; D005493:Folic Acid Antagonists; D011799:Quinazolines; D013876:Thiophenes; D013940:Thymidylate Synthase; C068874:raltitrexed; D005472:Fluorouracil