Necitumumab is an intravenously administered recombinant monoclonal IgG1 antibody used to treat metastatic squamous non-small cell lung cancer. It is approved for use in combination with cisplatin and gemcitabine. It blocks other ligands of the EGFR from binding and activating numerous signalling cascades to promote cell growth, proliferation, and differentiation. The main cascades that are affected are the MAPK signalling cascade, which affects the synthesis of DNA for proliferation and differentiation and the PI3K/AKT1 signalling cascade which also affects proliferation but also controls apoptosis. MAPK is activated through the epidermal growth factor receptor on the cell membrane and goes on to phosphorylate and regulate the activities of several transcription factors affecting cellular growth and proliferation. The PI3K/AKT1 signalling cascade is apart of the PI3K/AKT1/mTOR pathway which is an intracellular signalling pathway that also helps regulate the cell cycle. This signalling cascade can affect the regulation and activity of transcription factors as well. In cancer, the PI3K/AKT1/mTOR is overactive reducing apoptosis and allowing excessive cellular proliferation.

Necitumumab Pathway References