Fig. 2.
EGFR signaling through the PI3K/Akt pathway. Erlotinib and gelfitinib interfere with autophosphorylation of EGFR. In tumors that exhibit upregulation of IGFR, signaling of that receptor through Ras/Raf can bypass the block and generate sufficient activated PI3K to signal through Akt; these tumors are therefore resistant to erlotinib and gelfitinib. Adjunctive treatment with farnesyl transferase inhibitors or nelfinavir can overcome this resistance.