We investigated literature evidence regarding the putative cross-talks between EGFR/ErbB signaling and other signaling pathways. We found AKT2:MAML2 (in Reactome and KEGG), AKT2:TP53 (in Reactome), AKT2:MYC (in Reactome), KIT:MAML2 (in Reactome), KIT:TP53 (in Reactome), MDM2:MAML2 (in Reactome and WikiPathway), MDM2:TP53 (in Reactome), and TP53:MAML2 (in WikiPathway) gene-pairs as putative cross-talks between EGFR/ErbB signaling and Notch signaling pathways. Up-regulation of the Notch signaling pathway inhibits apoptosis and thus contributes to breast carcinogenesis [37]. The Notch signaling pathway cross-talks with EGFR/ErbB signaling at the mediator level [1], e.g. when activated, Notch1 contributes to cell growth and survival via Akt-activation in melanoma [38]. The Notch1 co-activator complex binds to the HES1 promoter [39] which encodes a transcription repressor that represses the expression of PTEN, a PI3K/Akt pathway inhibitor [40] contributing to tyrosine kinase inhibitor (TKI) resistance. Furthermore, Notch1 stimulates MYC transcription [41] and this stimulation can lead to the down-regulation of MYC via the Akt-pathway [42,43]. This putative gene-pair, AKT2:MYC was also found in our results as a potential drug-resistant cross-talk between the EGFR/ErbB and TGF- β receptor signaling pathways. Again, in HER2/neu-mediated resistance to DNA-damaging agents, the Akt pathway becomes activated which eventually suppresses p53 functions via enhancing MDM2-mediated ubiquitination [44]. Protein-protein interaction between MDM2 and p53 is evident as contributing to various cancer related activities [45,46].