Abstract 1947: Rovalpituzumab tesirine as a therapeutic agent for neuroendocrine prostate cancer
| Autor: | Etienne Dardenne, David M. Nanus, Michael Sigouros, Laura Saunders, Himisha Beltran, Loredana Puca, Verena Sailor, Kumiko Isse, Juan Miguel Mosquera, Katie Gavyert, Scott T. Tagawa |
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| Rok vydání: | 2018 |
| Předmět: |
Prostate adenocarcinoma
Cancer Research biology business.industry 05 social sciences Cancer Rovalpituzumab tesirine 030204 cardiovascular system & hematology medicine.disease 03 medical and health sciences Prostate cancer 0302 clinical medicine Oncology In vivo 0502 economics and business Cancer research biology.protein Medicine Adenocarcinoma Immunohistochemistry 050211 marketing Antibody business |
| Zdroj: | Cancer Research. 78:1947-1947 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2018-1947 |
| Popis: | Background: Delta-like protein 3 (DLL3) is expressed on the surface of small cell lung cancer (SCLC) tumor-initiating cells, and the DLL3 targeted antibody-drug conjugate, Rovalpituzumab tesirine (Rova-T™; SC16LD6.5), has shown promise for patients with SCLC. Neuroendocrine prostate cancer (NEPC) is an emerging late stage subtype of castration resistant prostate cancer with limited therapeutic options. Based on clinical and molecular similarities with SCLC, we investigated expression of DLL3 and the use of Rovalpituzumab tesirine in NEPC xenografts. Methods: We evaluated mRNA and/or protein expression of DLL3 in a cohort of 361 patients (552 samples) ranging from benign prostate (BEN), localized prostate adenocarcinoma (PCA), castration resistant adenocarcinoma (CRPC), and castration resistant NEPC and correlated with pathologic and genomic features. mRNA was assessed by RNAseq. Protein was assessed by immunohistochemistry (DLL3 SP347 antibody). Prostate cancer cell lines were engrafted in mice and treated with SC16LD6.5 in vivo. Results: DLL3 was expressed at the mRNA and/or protein level in 0/132 Benign (0%), 1/254 (0.4%) PCA, 10/90 (11.1%) CRPC and 47/76 (61.8%) NEPC samples. DLL3 IHC was of higher intensity in NEPC and co-localized with classical neuroendocrine (NE) markers. DLL3 was amongst the most differentially expressed genes by RNA-seq in NEPC versus CRPC (p= Conclusions: DLL3 is expressed on the surface of the majority of NEPC cases evaluated and is not expressed in primary prostate cancer or benign tissues. Modulation of DLL3 expression does not appear to affect AR or NEPC signaling in cell lines. SC16LD6.5 (Rova-T) demonstrates preferential preclinical activity in NEPC that express DLL3 compared to CRPC-adenocarcinoma that are DLL3 negative, in vivo. A Phase 1 Basket trial investigating Rova-T is now open with a dedicated NEPC arm (NCT02709889). Citation Format: Loredana Puca, Verena Sailor, Katie Gavyert, Etienne Dardenne, Kumiko Isse, Michael Sigouros, David M. Nanus, Scott T. Tagawa, Juan Miguel Mosquera, Laura Saunders, Himisha Beltran. Rovalpituzumab tesirine as a therapeutic agent for neuroendocrine prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1947. |
| Databáze: | OpenAIRE |
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