Therapeutics: Anaplastic lymphoma kinase (ALK); EML4-ALK oncogenic fusion protein; MAP kinase kinase 1 (MAP2K1; MEK1); MAP2K2 (MEK2)

Cell culture and mouse studies suggest combining inhibitors of ALK, MAP2K1 and MAP2K2 could help treat lung cancers positive for the EML4-ALK oncogenic fusion protein. In human lung adenocarcinoma cell lines harboring the EML4-ALK oncogenic fusion protein, ceritinib plus a subtherapeutic dose of trametinib decreased tumor growth compared with either agent alone. In a mouse xenograft model of lung adenocarcinoma harboring the fusion protein, ceritinib and a subtherapeutic dose of trametinib decreased tumor growth and disease recurrence compared with ceritinib alone. Next steps include clinical testing of combined ALK and MAP2K1/MAP2K2 inhibition as first-line therapy in lung cancer patients.

Novartis AG markets Zykadia ceritinib, an oral small molecule ALK inhibitor, to treat ALK-positive non-small cell lung cancer (NSCLC)...