The combination’s (dual) targeting of the same HER2 receptor at different points – ‘above’ and ‘below’ the cell membrane (vertical) – is known as vertical dual blockade:

• Trastuzumab is a monoclonal antibody that binds to the extracellular (‘above’) domain of the HER2 receptor.⁴
• Lapatinib, in contrast, inhibits kinase activity of the same HER2 receptor intracellularly (‘below’).⁴

By targeting both extracellular and intracellular domains of the same receptor – vertical dual HER2 blockade – complementary mechanisms of action may be realised, potentially achieving better pathway inhibition than could be accomplished with either compound alone.⁴