However, it has been found that the efficacy of PI3K-targeting agents might be inadequate to treat some patients with refractory resistance even when combined with the MEK inhibitor trametinib, and this lack of efficacy might be caused by differential compensation mechanisms that confer resistance to PI3K inhibitors in PIK3CA-amplified head and neck cancer cells [40]. This evidence concerns the gene MAP2K7 and head and neck cancer.