[Biomarkers and anti-EGFR therapies for KRAS wild-type tumors in metastatic colorectal cancer patients].
The natural history of metastasic colorectal cancer has being clearly modified in terms of response rate, time to progression and overall survival, once the antiEGFR monoclonal antibodies (cetuximab and panitumumab) have emerged in combination with the standard cytotoxic chemotherapy (FOLFOX and FOLFIRI). However, the benefit from cetuximab and panitumumab is only confined to KRAS-wild type (KRAS-wt) colorectal tumors, while KRAS-mutated tumors do not respond to these drugs. The 65% of colorectal tumors are KRAS-wt tumors, but efficacy of antiEGFR therapies is detected only in 60-70% of these KRAS-wt tumors. Other biomarkers and molecular pathways must be involved in the response of the antiEGFR therapies for the KRAS-wt colorectal tumors, such as the EGFR ligands, the EGFR-phosphorilated levels, the number of EGFR copies, the status of the KRAS effecter B-RAF and the alternative intracellular signaling pathways PIK3CA/PTEN/AKT and JAK/STAT. A battery of these biomarkers is needed to select the most sensitive patients to the antiEGFR therapies. This pattern may represent a novel favorable cost-effectiveness tool to develop tailored treatments. A review of these biomarkers and molecular pathways, involved in the antiEGFR therapies response, is performed.
Díaz-Rubio García
Eduardo
E
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D011905:Genes, ras; D006801:Humans; D009362:Neoplasm Metastasis; D000077544:Panitumumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015415:Biomarkers; D000077544:Panitumumab; D066246:ErbB Receptors; D000068818:Cetuximab