Molecular biology of esophageal cancer.

Published

Journal Article (Review)

Several mechanisms of resistance to chemotherapy have been identified among the agents that are commonly used in the systemic treatment of patients with esophageal cancer: paclitaxel, platinum, and 5-FU. A recent study from our laboratory evaluated the initial endoscopic biopsy material from patients who subsequently underwent trimodality therapy, including chemotherapy with cisplatin and 5-FU, radiation therapy, and surgery. IHC analysis was performed on seven markers of chemotherapy or radiation therapy resistance: P-gp, GST-pi, MT (platinum inhibitors); EGF-R, TGF-alpha, erb-B2 (activation of cell growth cascade); and p53 (interferes with chemotherapy-induced apoptosis). In this study, elevated expression of GST-pi and P-gp were associated with decreased survival and may be markers of treatment resistance. Expression of erb-B2 was associated with enhanced survival and may be a marker of treatment sensitivity. Assessment of the probability of chemoresistance of a particular tumor using the expression of molecular biologic markers may allow for the selection of a more favorable chemotherapeutic agent. Furthermore, understanding the mechanisms of resistance, including the mechanisms of DNA repair, may provide insight into mechanisms to reverse or to inhibit resistance to chemotherapy. DNA repair mechanisms are used by cells to protect themselves against mutagens and carcinogens. DNA repair inhibitors may increase the mutagenicity associated with DNA damage and may prove to be an ineffective oncologic treatment strategy; however, the possibility exists that DNA repair inhibition may improve the efficacy of anticancer agents, and this should be tested. The value of this strategy may be in allowing treatment doses to be decreased and lessening side effects while maintaining therapeutic efficacy.

Full Text

Duke Authors

Cited Authors

  • D'Amico, TA; Harpole, DH

Published Date

  • August 2000

Published In

Volume / Issue

  • 10 / 3

Start / End Page

  • 451 - 469

PubMed ID

  • 10967750

Pubmed Central ID

  • 10967750

International Standard Serial Number (ISSN)

  • 1052-3359

Language

  • eng

Conference Location

  • United States