Targeted inhibition in tumors with ALK dependency

rgeted inhibition in tumors with ALK dependency Review (706) Total Article Views Authors: Kwak EL, Clark JW, Shaw AT Published Date January 2013 Volume 2013:4 Pages 1 - 8 DOI: http://dx.doi.org/10.2147/LCTT.S16313 Received: 13 March 2012 Accepted: 23 October 2012 Published: 10 January 2013 Eunice L Kwak, Jeffrey W Clark, Alice T Shaw Massachusetts General Hospital Cancer Center, Boston, MA, USA Abstract: The oncogenic function of gene translocations involving the anaplastic lymphoma kinase (ALK) was first reported in rare subtypes of non-Hodgkin's lymphoma almost two decades ago. More recently, aberrant ALK signaling was found to be an oncogenic driver in subsets of non-small cell lung cancer (NSCLC), particularly in patients with little or no tobacco smoking history. The advent of molecularly targeted therapies that inhibit ALK has allowed the pairing of ALK inhibitors such as crizotinib as treatment for ALK-positive NSCLC, yielding dramatic responses and long-term disease control. The clinicopathologic features of ALK-driven NSCLC, the clinical development of ALK inhibitors, and the genetic determinants of acquired resistance to ALK inhibition are among the topics covered in this review.