Predictive biomarkers with potential of converting conventional chemotherapy to targeted therapy in patients with metastatic colorectal cancer

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Niels Frank Jensen
  • David Hersi Smith
  • Sune Boris Nygård
  • Maria Unni Koefoed Rømer
  • Kirsten Vang Nielsen
  • Brünner, Nils
Abstract The availability of systemic chemotherapy regimens for the treatment of patients with metastatic colorectal cancer (mCRC) is based on the results from large prospective, randomized studies. The main chemotherapeutic drugs used in treatment of mCRC are the fluoropyrimidines (5-fluorouracil (5-FU); capecitabine) in combination with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI). The objective response rate to either combination is approximately 50%, where no significant differences with regard to progression free survival or overall survival have been observed. Interestingly, a number of preclinical and clinical studies have indicated lack of full cross resistance between oxaliplatin based and irinotecan based treatment. Therefore, it is possible that certain mCRC patient subpopulations would benefit more from one drug combination rather than the other. To address this clinical problem there has been much focus on development and validation of predictive biomarkers for these three drugs. Here, we present a thorough review on the current status of predictive biomarkers for 5-FU, oxaliplatin and irinotecan treatment of mCRC patients. The overall conclusions were as follows: Several promising biomarker candidates were identified, notably thymidylate synthase for 5-FU, topoisomerase I for irinotecan and ERCC1 for oxaliplatin. However, these candidates warrant further analysis, where assay performance and clinical trial design should be in focus.
OriginalsprogEngelsk
TidsskriftScandinavian Journal of Gastroenterology
Vol/bind47
Udgave nummer3
Sider (fra-til)340-355
Antal sider16
ISSN0036-5521
DOI
StatusUdgivet - 2012

    Forskningsområder

  • Det tidligere LIFE - 5-fluorouracil, irinotecan, metastatic colorectal cancer, oxaliplatin, predictive biomarkers

ID: 37551622