Patients were appraised by a review of data from a prospective re-biopsy protocol for lung malignancy patients with an EGFR-mutated phenotype with acquired resistance to EGFR-TKI therapy. phenotype with acquired resistance to EGFR-TKI therapy. Of 100 patients, 49 and 21 patients carried high and low level of CEA, respectively; 30 carried normal CEA. Median progression-free survival was 6.4 and 4.5 months in patients with high and low level of CEA, respectively (P=0.027). Median PFS of patients in low-CEA group longer than that of those with normal level of tumors (3.0 months; P=0.002). The difference between groups L and N was not significant regarding objective response rate and overall survival. No significant difference was found in three groups of acquired resistance to EGFR-TKIs. The relative CEA level could predict benefit of EGFR-TKI therapy in advanced NSCLC, but could not predict acquired resistance to EGFR-TKIs. (24) and Jung (23) reported that patients treated with EGFR-TKI with higher CEA levels experienced a longer survival and a better response than those with low CEA Duloxetine levels. Shoji (36) reported that this rate of EGFR gene mutation is usually significantly increased as the levels of CEA increases (for the levels of CEA of 5, 5 but 20 and 20 the rate of EGFR gene mutation was 35, 55 and 87.5%, respectively; P=0.040). Their study presented a significant association between EGFR gene mutations and the levels of CEA in patients with lung adenocarcinomas. To the best of the authors’ knowledge, little is known about the function of CEA. Wirth (37) reported that CEA can inhibit the apoptosis and has prometastatic roles in colon cancer cells, and Ordonez (38) also reported that the overexpression of CEA can protect tumor cells from apoptosis and inhibit cell death. EGFR mutations were detected within an ATP binding pocket Duloxetine with catalytic domain, and the mutants also had an enhanced tyrosine kinase activity in response to the ligand. In addition, the present studies have demonstrated that such downstream molecules as Akt and STAT3 serve a crucial role in the antiapoptotic pathways of EGFR mutations in tumor cells (39). Moreover, the mutated EGFRs are autophosphorylated in the absence of interleukin-3 without EGF stimulation, and their expression leads to the STAT5 activation and the upregulation of the extracellular signal-regulated kinase 1 or 2 2 (Erk1 or 2), Erk5 and Akt (40). It is hypothesized that this continuous signal of the mutant EGFR can stimulate antiapoptotic activity in a ligand-independent manner. Thus, overexpression of the CEA protein as antiapoptotic Duloxetine may be observed in patients with EGFR mutants. In the present study, the median OS of patients were 11.9, 9.4 and 7.8 months, respectively, in groups H, L and N. Similar to the ORR, the difference in the median OS between groups H and N and between groups H and L were significant (P 0.001 and P=0.022, respectively), whereas these between groups L and N were not (P=0.115). In addition, the multivariate analysis revealed that group H was an independent positive predictive factor for PFS (HR, 1.25; 95% CI, 1.09C1.39). Considering histologic heterogeneity in NSCLC, the authors hypothesized that the serum CEA level in patients with pretreated lung cancer partly represents the extent of the mutant EGFR component in the lung cancer. This hypothesis may partially explain why the effect durations were not as long as expected in some patients with EGFR mutations. By determining the serum CEA level, one could select the patients with high serum CEA levels for EGFR-TKIs treatment to guarantee the best therapy effect. Importantly, more attention should be paid to patients with low serum CEA levels while making therapeutic KRT13 antibody strategies, it is necessary for them to give combined strategies, rather than single administration of EGFR-TKIs. With regard to the potential benefit of learning about a small cell histologic transformation, as well as the prognostic value of EGFR T790M mutation, the authors biopsy patients at the time of development of acquired resistance as part of routine consideration. These data demonstrate that there were no differences between the patients with low serum CEA and the patients who had high serum CEA. It is presumed that the level of CEA could not predict acquired resistance to EGFR-TKIs. In summary, the present study suggests that the relative pre-therapeutic CEA level can predict the extent of benefits from EGFR-TKIs, but can not predict the acquired drug resistance to EGFR-TKIs therapy in patients with EGFR mutations. However, the current study is believed.
