Insights into ALK biology to unravel novel therapeutic pathways
Claudia Voena
Center for Experimental Research and Medical Studies (CeRMS) University of Torino
The Anaplastic Lymphoma Kinase (ALK) is the “driver” oncogene of several tumor types, including Anaplastic Large Cell Lymphoma (ALCL), Non-Small Cell Lung Cancer (NSCLC), Inflammatory Myofibroblastic tumors (IMT) and Neuroblastoma (NB). Most prevalent ALK alterations are chromosomal rearrangements resulting in fusion genes, as seen in ALCL and NSCLC. In other tumors, activating ALK mutations (i.e. NB) and ALK copy-number gains have been described. Translocated ALK was originally found in ALCL in 1994. ALCL is the most common TCL, representing ~10% of all peripheral lymphomas in children and 3% of adult Non-Hodgkin Lymphoma. In ALCL oncogenic ALK is constitutively active and contributes to lymphomagenesis and maintenance of neoplastic phenotype. Inhibition of ALK kinase activity is the key to treating ALK+ ALCL. However, ALK tyrosine kinase inhibitors (TKI) can induce remission but not cure. We have extensively studied the role of ALK in lymphoma and other ALK-driven cancer by discovering multiple pathways exploited to induce cellular transformation and to define new therapeutic vulnerabilities and to find innovative treatments.
In this seminar I will discuss new insights into the biology of ALK signaling in ALK-driven cancer.