ABSTRACT
This chapter focuses on anaplastic lymphoma kinase (ALK)/ROS1 mutant patients and on how a better understanding of this particular sub-type of non-small cell lung has led to the very rapid development of novel and effective systemic therapies. Patients with stage IV lung adenocarcinoma should be assessed for ALK gene rearrangements, regardless of smoking history. ALK, although very rarely, should be offered also in non-adenocarcinoma histology. Immunohistochemistry is a reliable and relatively easy diagnostic tool to detect pathologic proteins in paraffin-embedded tissues without the loss of the cytologic and architectural features. Progression on crizotinib occurs with relatively high frequency in the central nervous system (CNS)-only, which is likely related to crizotinib’s poor CNS penetration. Systemic progression outside of the CNS may occur in patients receiving crizotinib and can occur through the emergence of secondary crizotinib resistant ALK mutations, which are found in 20% of patients. Alectinib is a tyrosine kinase inhibitor with the advantage of affecting several ALK mutations that confer resistance to crizotinib.
