Mutant forms of the protein EGFR are important for the development of lung cancer in a substantial proportion of individuals with this disease. However, not all individuals express the same mutant EGFR, for example, some have a mutation that affects the intracellular part of EGFR and some have a mutation that affects the extracellular part of EGFR (known as the EGFRvIII mutant).
The potential of therapeutics to benefit individuals with lung cancer caused by the distinct EGFR mutants can be examined using two mouse models of lung cancer, one driven by expression of EGFR with a mutation in the intracellular part of the protein and one driven by expression of the EGFRvIII mutant.
In a study appearing online on January 25 in advance of publication in the February print issue of the Journal of Clinical Investigation, Kwok-Kin Wong and colleagues from the Dana-Farber Cancer Institute in Boston show that a mouse antibody that binds EGFR (mAb806) causes the regression of lung tumors in both models of lung cancer. By contrast, a second antibody that binds EGFR (cetuximab), and that is already in clinical use for the treatment of a specific subset of patients with lung cancer, only induced tumor regression in mice with lung tumors driven by expression of EGFR with a mutation in the intracellular part of the protein. Importantly, the humanized form of mAb806 (ch806) caused regression of lung tumors in both models of lung cancer. The data presented in this study therefore indicate that ch806 might provide a new therapeutic for the treatment of patients with lung cancer driven by mutant forms of EGFR, in particular the EGFRvIII mutant.