Our results indicated that failure of dual EGFR HER2 inhibition to induce apoptosis resulted from the failure of the same drugs to downregulate Akt phosphorylation. In support, AG879 and AG1478 in combination wasn’t effective in inducing apoptosis Cyclopamine clinical trial in LNCaP AI cells in the presence of control siRNA, while Akt siRNA alone induced a significant increase in Annexin V staining which was further increased in the presence of the drugs. Previous studies showed the double EGFR/HER2 chemical lapatinib evidenced no reduction in PSA in patients with hormone sensitive PCa or in unselected patients with CRPC. The goal of this study was to determine whether double EGFR/HER2 inhibition has any role in preventing illness progression in PCa. We show that androgendependent PCa cells with low ErbB action don’t show large response to ErbB inhibitors, whereas throughout AWT, ErbB2 and ErbB3 amounts Plastid increase, which oversees cell survival Akt phosphorylation and also. Therefore, during this time period, when the increase in these receptors is inhibited by twin EGFR/ErbB2 inhibition, which also inhibits ErbB3 phosphorylation, the increase in Akt phosphorylation and success could be avoided. Nevertheless, once ErbB3 levels have increased, the same drugs fail to affect the levels of Akt phosphorylation, thereby suggesting that they can inhibit de novo activation of ErbB3 but cannot dephosphorylate the receptor after it is activated. The entire impact of dual inhibition was similar, though person EGFR and HER2 inhibitors had differential effects on PCa cells. The difference between various inhibitors of the same receptor might be attributed to the power of the binding of these inhibitors to the receptor. We observe that in both cases, the drug combinations triggered a reduction in Akt phosphorylation. The ErbB dimers formed within this disease include EGFR homodimers and HER2 ErbB3, EGFR HER2 and EGFR ErbB3 heterodimers, since ErbB4 is Aurora Kinase Inhibitors dropped in PCa. All subscribe to survival of PCa cells, ergo inhibition of only 1 receptor will not prevent downstream signaling. Our data demonstrates inhibition of both EGFR and HER2 is required to avoid ErbB3 signaling, likely by blocking its dimerization. The majority of the Akt signaling might be downstream of ErbB3 dimerization with EGFR or HER2, that will be inhibited only upon dual inhibition, since only ErbB3 but not EGFR or HER2 have p85 PI3K binding sites. ErbB3 monoclonal antibodies such as MM 121 are currently in progress, and are also prone to achieve mixture with other ErbB inhibitors such as lapatinib. We demonstrate that in cells expressing high AR, either hormone na?ve cells never confronted with AWT, or in CRPC cells that have high AR transcriptional exercise, dual ErbB inhibition is not able to prevent Akt phosphorylation and cell survival.