Evaluation of RET Tyrosine Kinase as a Novel Driver of Prostatic Small Cell Neuroendocrine Carcinoma.

摘要

Prostate cancer is the most common diagnosed and second leading cause of epithelial cancer-related death in men. Small cell neuroendocrine carcinoma (SCNC) accounts for only 1% of diagnosed prostate cancers prior to aggressive therapy. However, after administration of aggressive therapy, tumor resistance is inevitable resulting in the acquisition of SCNC tumors in well over 20% of patients. SCNC tumors are highly aggressive, metastasize readily, and often lead to death of the patient within months after diagnosis. Tyrosine kinases represent an untapped area for therapy in the stratification of SCNC patients. We observed that RET tyrosine kinase is heightened at the mRNA and protein level in SCNC tissues and neuroendocrine cell lines when compared to adenocarcinoma. RET expression and related neuroendocrine markers were upregulated in a model of neuroendocrine differentiation and RET mutations resulted in initiation of prostate cancer. Future work will continue to define the role of RET in prostate cancer.