4126 Background: KRAS mutations have been implicated in the resistance of CRC to cetuximab (Lievre et al, J Clin Oncol, 2007) and key mechanisms involved in the resistance to anti-EGFR therapy appear to come from the constitutive activation of EGFR downstream signaling. Methods: EGFR downstream signaling phosphoproteins expression, belonging to MAP kinase (p-MEK, p- ERK1/2) and AKT (p-AKT, p-GSK3, p-P70S6K) pathways were analyzed using Bioplex phosphoprotein array in 42 patients treated for advanced CRC by cetuximab (41) or panitumumab (1) then confronted to KRAS mutation previously analyzed. Results: Among the 42 patients analyzed (M/F: 24/18; mean age: 61.8 years), 12 (28.5%) had an objective response to anti EGFR antibodies (CR: 1, PR: 11), administered in monotherapy (n=3) or in combination with irinotecan (alone, n=37; FOLFIRI regimen, n=2). Median progression-free survival (PFS) was 15.3 weeks. KRAS mutations were observed in 45.2% of the cases (n=19) and were significantly associated with the absen...