Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer with poor prognosis, and there is a critical need for novel therapeutic approaches. NEPC is associated with molecular perturbation of several pathways, including amplification of MYCN. Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase involved in the pathogenesis of neuroblastoma and other malignancies where it cooperates with N-Myc. We previously identified the first case of ALK F1174C-activating mutation in a patient with de novo NEPC who responded to the ALK inhibitor, alectinib. Here, we show that coactivation of ALK and N-Myc (ALK F1174C/N-Myc) is sufficient to transform mouse prostate basal stem cells into aggressive prostate cancer with neuroendocrine differentiation in a tissue recombination model. A novel gene signature from the ALK F1174C/N-Myc tumors was associated with poor outcome in multiple human prostate cancer datasets. ALK F1174C and ALK F1174C/N-Myc tumors displayed activat..... READ ARTICLE
Cancer Research DOI:10.1158/0008-5472.CAN-20-3351
Authors: Kenji Unno, Zachary R. Chalmers, Sahithi Pamarthy, Rajita Vatapalli, Yara Rodriguez, Barbara Lysy, Hanlin Mok, Vinay Sagar, Huiying Han, Young A. Yoo, Sheng-Yu Ku, Himisha Beltran, Yue Zhao and Sarki A. Abdulkadir
