Methods and compositions for use of growth factor antibodies in combination with non-tyrosine targeting kinase inhibitors

A method of treating non-small cell lung carcinoma (NSCLC) or colorectal cancer (CRC) in a subject, comprising the steps of:

• administering to the subject a non-tyrosine targeting kinase inhibitor (NTKI) that inhibits one or more kinases involved in intracellular signaling initiated by epidermal growth factor (EGF), and a non-natural synthetic polypeptide (NNSP), wherein the NNSP comprises a polypeptide comprising an amino acid sequence at least 95% identical to SEQ ID NO:
• 7 or SEQ ID NO:
• 8,
• an immunogenic polypeptide comprising a cholera toxin B (CT-B) protein, or a fragment thereof, and
• a linker, wherein the NNSP is separated from the immunogenic polypeptide by the linker optionally wherein the NNSP is from a cell that expresses SEQ ID NO:
• 7 or SEQ ID NO:
• wherein administration of the NNSP induces an immune response against EGF and reduces EGF-mediated receptor signaling, thereby delaying acquisition of resistance to the NTKI in the subject.