Panitumumab is indicated for the treatment of patients with metastatic colorectal cancer after failure of other cytotoxic drugs. Panitumumab is the first fully human monoclonal antibody directed against the epidermal growth factor receptor (EGF-R). The EGF-R plays an important role in all kinds of tumors and is one of the most important targets for growth hormones.
Panitumumab occupies the EGF-R thereby preventing its endogenous ligands epidermal growth factor (EGF) or transforming growth factor β (TGFβ) to bind. Panitumumab has no agonistic effects and induces internalisation of the EGF-R receptor. The intracellular processes that occur normally after activation of the EGF-R by its ligands (dimerisation, autophosphorylation and signal transduction) are now prevented by panitumumab binding. In the end, the
decreased expression of growth factors results in increased apoptosis and reduced proliferation of tumor cells and angiogenesis. Tumor growth and development of metastases is prevented.
The most common adverse effects included eye, skin and gastrointestinal problems, which are related to the primary mode of action through the blockade of the EGF-R. Hypomagnesaemia, another common problem can be explained by the effect of panitumumab on tubular reabsorption of filtered magnesium in the kidney and magnesium absorption in the GI tract.
Cetuximab is also known for its EGF-R blocking effects. This antibody is half human, half murine. Erlotinib is another tumor suppressing drug that acts at the tyrosine kinase of the EGF-R and preventing the autophosphorylation.
EPAR of panitumumab.