Targeting ALK, ROS1, and BRAF Kinases

Abstract

As the repertoire of targetable genetic abnormalities increase, we will need to develop mechanisms that are both practi-cal and reliable to identify patients with relatively rare oncogenes. The broad range of crizotinib- resistance mechanisms observed in ALK NSCLC suggests that diversity will re-emerge as a major issue even from initially largely molecular uniform tumors in the acquired-resistance setting. Whether therapies directed against resistance mechanisms should be employed only at the time of resistance, or earlier to delay the emergence of resistance, will need to be addressed over the next few years. Factors influencing the choice between these two strategies will include the tolerabil-ity of the treatment regimen and whether technology looking, for example, for low levels of resistance mechanisms in treatment-naive patients, will evolve to allow us to accurately predict which patient is more likely to employ a specific mechanism of resis-tance before it becomes clinically apparent. © 2012 by the International Association for the Study of Lung Cancer.