Phosphorylated AKT and MAPK expression in primary tumours and in corresponding metastases and clinical outcome in colore
- PDF / 304,441 Bytes
- 10 Pages / 595.28 x 793.7 pts Page_size
- 16 Downloads / 143 Views
RESEARCH
Open Access
Phosphorylated AKT and MAPK expression in primary tumours and in corresponding metastases and clinical outcome in colorectal cancer patients receiving irinotecan-cetuximab Mario Scartozzi1*, Riccardo Giampieri1, Elena Maccaroni2, Alessandra Mandolesi3, Simona Biagetti3, Simona Alfonsi3, Lucio Giustini4, Cristian Loretelli1, Luca Faloppi2, Alessandro Bittoni2, Maristella Bianconi2, Michela Del Prete2, Italo Bearzi3 and Stefano Cascinu1
Abstract Background: Clinical observations suggested that a non negligible proportion of patients, ranging from 40% to 70%, does not seem to benefit from the use of anti-EGFR targeted antibodies even in the absence of a mutation of the K- RAS gene. The EGFR pathway activation via the Ras-Raf-MAP-kinase and the protein-serine/threonine kinase AKT could determine resistance to anti-EGFR treatment. Methods: We tested the interaction between phosphorylated AKT and MAPK expression in colorectal tumours and corresponding metastases and global outcome in K-RAS wild type patients receiving irinotecan-cetuximab. Results: Seventy-two patients with histologically proven metastatic colorectal cancer, treated with Irinotecan and Cetuximab based chemotherapy, were eligible for our analysis. In metastases pAKT correlated with RR (9% vs. 58%, p = 0.004), PFS (2.3 months vs.9.2 months p < 0.0001) and OS (6.1 months vs.26.7 months p < 0.0001) and pMAPK correlated with RR (10% vs., 47%, p = 0.002), PFS (2.3 months vs.8.6 months p < 0.0001) and OS (7.8 months vs.26 months p = 0.0004). At multivariate analysis pAKT and pMAPK in metastases were able to independently predict PFS. pAKT in metastases independently correlated with RR as well Discussion: pAKT and pMAPK expression in metastases may modulate the activity of EGFR-targeted antibodies. We could speculate that in patients with pAKT and pMAPK metastases expression targeting these factors may be crucial. Keywords: Phosphorylated AKT, Phosphorylated MAPK, Liver metastases, Cetuximab, Colorectal cancer, K-RAS
Background Monoclonal antibodies against the ligand-binding site of the epidermal growth factor receptor (EGFR) have been shown to improve global outcome of metastatic colorectal cancer patients [1-5]. The introduction of K-RAS mutational status for patients selection in this setting appeared to possess the necessary potential for a full translation into clinical practice of the concept of targeted therapy [5-7]. * Correspondence: [email protected] 1 Clinica di Oncologia Medica, AO Ospedali Riuniti-Università Politecnica delle Marche, Marche Via Conca, Ancona, 60020, Italy Full list of author information is available at the end of the article
In fact although we are now able to exclude from antiEGFR treatment patients with putative refractory colorectal tumours (i.e. those harboring a K-RAS mutant status), we are still unable to select responding patients among those without K-RAS mutations. Clinical observations suggested that a non negligible proportion of patients, ranging from 40% to 70%, does not seem to benefit
Data Loading...
