ALK gene alterations in cancer: biological aspects and therapeutic implications.

ABSTRACT

ALK was first reported in 1994 as a translocation in anaplastic large cell lymphoma and then described with different abnormalities in a number of tumors. Recently, a shortly accumulated biomedical research clarified the numerous biological processes underlying its ability to support cancer development, growth and progression. Advent of precision medicine has finally provided unexpected advances, leading to the development of ALK-targeting inhibitors with superior efficacy as compared with standard chemotherapy regimens, as well as the identification of resistance mechanisms and the creation of 'next-generation' treatments. This review summarizes the current understanding of ALK-driven cancers from the oncogenesis and mutation frequency by The Cancer Genome Atlas database through the diagnostic approach, to an updated portrait of available tyrosine kinase inhibitors, considering their effectiveness in cancer treatment, the molecular reasons of therapeutic failure, and the actual and future ways to overcome resistances.