Topoisomerase I expression correlates to response to neoadjuvant irinotecan-based chemoradiation in rectal cancer

Anticancer Drugs. 2009 Jul;20(6):519-24. doi: 10.1097/CAD.0b013e32832b53ff.


Biomarkers may help predict the efficacy of neoadjuvant chemoradiation in patients with rectal cancer. We hypothesized that the expression of topoisomerase I (Topo I) and thymidylate synthase (TS) may help predict the treatment response in patients undergoing irinotecan and capecitabine-based chemoradiation. Patients with rectal cancer (cT3/4Nx or Tx/N+) received neoadjuvant chemoradiotherapy within clinical studies with irinotecan and capecitabine. Samples of normal and tumour tissues were collected before the start of the treatment and during surgical resection. Topo I and TS were measured using real-time PCR. The results of gene expression levels were compared between responders (defined as ypT0-2 ypN0) and nonresponders (ypT3-4 or ypN1/2). A total of 38 patients were analysed, 18 of them were responders. The biopsies of the untreated tumour tissue of responding patients showed a significant higher expression of Topo I compared with nonresponding patients (P = 0.015). Normal tissue did not show this difference (P = 0.126). During chemoradiation, the Topo I expression in tumour tissue of responders decreased significantly. TS did not show any differences between responders and nonresponders before treatment, but a significant decrease in the tumour tissue of responders was noted at the end of the treatment. Our data suggest that Topo I expression in rectal tumour mucosa might serve as a predictor of response to the neoadjuvant irinotecan-based chemoradiation, and hence might be a factor contributing to the development of individualized treatment.

Publication types

  • Clinical Trial

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / biosynthesis*
  • Biopsy
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • DNA Topoisomerases, Type I / biosynthesis*
  • Humans
  • Intestinal Mucosa / enzymology
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / surgery
  • Irinotecan
  • Neoadjuvant Therapy* / methods
  • Neoplasm Invasiveness
  • Prospective Studies
  • Rectal Neoplasms / drug therapy*
  • Rectal Neoplasms / enzymology
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / radiotherapy*
  • Rectal Neoplasms / surgery
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thymidylate Synthase / biosynthesis


  • Biomarkers, Tumor
  • Irinotecan
  • Thymidylate Synthase
  • DNA Topoisomerases, Type I
  • Camptothecin