Delta-like protein 3 expression and therapeutic targeting in neuroendocrine prostate cancer

著者: Loredana Puca, Katie Gavyert, Verena Sailer, Vincenza Conteduca, Étienne Dardenne, Michael Sigouros, Kumiko Isse, Megan Kearney, Aram Vosoughi, Luisa Fernandez, Heng Pan, Samaneh Motanagh, Judy Hess, Adam Donoghue, Andrea Sboner, Yuzhuo Wang, Ryan Dittamore, David S. Rickman, David M. Nanus, Scott T. Tagawa, Olivier Elemento, Juan Miguel Mosquera, Laura R. Saunders, Himisha Beltran - Science Translational Medicine 2019 被引用: 209

loss, and aggressive clinical features. DLL3 in circulating tumor cells was concordant with matched metastatic biopsy (87%). Treatment of DLL3-expressing prostate cancer xenografts with a single dose of SC16LD6.5 resulted in complete and durable responses, whereas DLL3-negative models were insensitive. We highlight a patient with neuroendocrine prostate cancer with a meaningful clinical and radiologic response to SC16LD6.5 when treated on a phase 1 trial. Overall, our findings indicate that DLL3 is preferentially expressed in CRPC-NE and provide rationale for targeting DLL3 in patients with DLL3-positive metastatic prostate cancer.