We then observed whether the above gene-pairs overlap with the list of potential cross-talks between EGFR/ErbB signaling and other signaling pathways. Here, we collected 24 signaling pathways from Reactome [32], 35 signaling pathways from KEGG [33,34], and 63 signaling pathways from WikiPathway [35] databases, and respectively identified 1,083 (841 distinct), 2,179 (1,050 distinct) and 3,084 (876 distinct) gene-pairs (Additional file 3: Table S2, Additionalfile 4: Table S3 and Additional file 5: Table S4) between EGFR/ErbB and other signaling pathways (seeMaterials and method). Of the 11,515 gene-pairs identified above, we found 104 (97 distinct), 188 (99 distinct) and 299 (96 distinct) gene-pairs overlap with the potential EGFR cross-talks identified using Reactome, KEGG and WikiPathway, respectively. Note the number of potential cross-talks and the number of distinct gene-pairs are different because the same gene-pair can form cross-talks between multiple pathway-pairs (pathways are overlapping). We consider these overlapping gene-pairs as putative drug-resistant cross-talks between EGFR/ErbB and other signaling pathways. In these 104, 188 and 299 cross-talks, we found candidate EGFR/ErbB cross-talks with 13, 26 and 51 other signaling pathways, respectively. Moreover, among all 104, 188 and 299 cross-talks from Reactome, KEGG and WikiPathway, respectively, we found 32 distinct gene-pairs in at least two of these sets. Primary findings and detailed descriptions of all these putative cross-talks from the analyses of all three pathway sources are listed in Table 1, and Additional file 6: Table S5, Additional file 7: Table S6 and Additional file 8: Table S7, respectively. The network views of all these cross-talk sets from the analyses of individual pathway sources are shown in Figure 2.