Prognostic molecular markers for planning adjuvant chemotherapy trials in Dukes' B colorectal cancer patients: how much evidence is enough?
The benefit of postoperative adjuvant chemotherapy in patients with Dukes' B colorectal cancer is still uncertain and its routine use is not recommended. Prognostic biomarkers may be useful for identifying high-risk patients with resected, node-negative disease, and this stratification may represent an innovative strategy for designing adjuvant chemotherapy trials. Featured prognostic molecular markers can be divided into the following categories: cell proliferation indices (Ki-67, Mib-1, proliferating cell nuclear antigen); oncogenes/tumor suppressor genes [p53, K-ras, Deleted in Colorectal Cancer (DCC), Bcl-2, c-erbB2]; DNA repair (microsatellite instability); markers of angiogenesis (vascular count, vascular endothelial growth factor); markers of invasion/metastasis (plasminogen-related molecules, matrix metalloproteinases); and biochemical markers (thymidylate synthase). Studies that have investigated their prognostic role in Dukes' B colorectal cancer patients are reviewed here. Current data do not provide sufficient evidence for the incorporation of available prognostic biomarkers into clinical practice. However, a biomarker-based approach could be an effective strategy for improving results of postoperative adjuvant treatments in high-risk Dukes' B colorectal cancer patients. Markers of altered DCC function have shown promising prognostic role and sufficient prevalence in retrospective investigations and they deserve further assessment in prospective studies.
Graziano
F
F
Medical Oncology Unit, Hospital of Urbino, Urbino, Italy. frada@tin.it
Cascinu
S
S
D014408:Biomarkers, Tumor / Q000032:analysis*; D002455:Cell Division / Q000276:immunology; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004260:DNA Repair; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D009857:Oncogenes; D010347:Patient Care Planning; D011379:Prognosis
D014408:Biomarkers, Tumor