A review on the use of molecular markers of cytotoxic therapy for colorectal cancer, what have we learned?
BACKGROUND
Over the past decades, significant progress has been achieved in the cytotoxic treatment of colorectal cancer (CRC) by the use of fluoropyrimidines, irinotecan and oxaliplatin. However, as not all patients do respond to chemotherapy, there is a need for predictive and prognostic factors in order to optimise the treatment for individual patients. Although many potential molecular markers have been studied, none of these have been implemented in the standard of care for colorectal cancer patients.


METHODS
We performed a review of the data on the prognostic and/or predictive value of molecular markers for cytotoxic drugs in CRC. The following markers were included: dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase, thymidine phosphorylase, thymidylate synthase, mismatch repair deficiency, topoisomerase 1, excision cross-complementing gene and carboxylesterases.


RESULTS
With the exception of mismatch repair deficiency, these molecular markers showed divergent and inconsistent results on their prognostic and/or predictive value. This underscores the complexity of the role of these markers.


CONCLUSIONS
We conclude that further retrospective testing of these markers is unlikely to add clinically useful results. More definite results may only be expected when these markers are included in the design of prospective randomised studies.
Koopman
Miriam
M
Department of Medical Oncology, Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Venderbosch
Sabine
S
Nagtegaal
Iris D
ID
van Krieken
Johan H
JH
Punt
Cornelis J
CJ
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D053843:DNA Mismatch Repair; D005472:Fluorouracil / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077146:Irinotecan; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D011379:Prognosis; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin