This project combines the expertise of three professionals – a chemical biologist who recently discovered a new and potent anticancer drug (ie, thailandepsin A [TDP-A]), a nanotechnologist/materials chemist who develops multifunctional drug nanocarriers for targeted cancer therapy, and a surgeon/neuroendocrine cancer biologist – to develop multifunctional nanomedicines for targeted carcinoid cancer therapy. At the completion of the project, we intend to demonstrate that TDP-A is a potent anticancer drug for carcinoid cancers and that tumor-targeting TDP-A loaded nanocarriers have the potential to significantly enhance the efficacy of therapeutic treatments in carcinoid cancers while minimizing any undesirable side-effects.
The investigators will conduct preclinical experiments to establish the feasibility of this new treatment strategy for treating patients with neuroendocrine cancers.
Jang S, Janssen A, Aburjania Z, Robers MB, Harrison A, Dammalapati A, Cheng Y-Q, Chen H, Jaskula-Sztul R. Histone deacetylase inhibitor thailandepsin-A activates Notch signaling and suppresses neuroendocrine cancer cell growth in vivo. Oncotarget. 2017 Sep 19; 8(41): 70828–70840. Published online 2017 Aug 7. doi: 10.18632/oncotarget.19993
Yu XM, Jaskula-Sztul R, Georgen MR, Aburjania Z, Somnay YR, Leverson G, Sippel RS, Lloyd RV, Johnson BP, Chen H. Notch1 Signaling Regulates the Aggressiveness of Differentiated Thyroid Cancer and Inhibits SERPINE1 Expression. Clin Cancer Res. 2016 Jul 15;22(14):3582-92. doi: 10.1158/1078-0432.CCR-15-1749. Epub 2016 Feb 4.
Jaskula-Sztul R, Chen G, Dammalapati A, Harrison A, Tang W, Gong S, Chen H. J Mater Chem B. AB3-Loaded and Tumor-Targeted Unimolecular Micelles for Medullary Thyroid Cancer Treatment. 2017 Jan 7;5(1):151-159. doi: 10.1039/C6TB02530G. Epub 2016 Dec 2.
Somnay YR, Yu XM, Lloyd RV, Leverson G, Aburjania Z, Jang S, Jaskula-Sztul R, Chen H. Notch3 expression correlates with thyroid cancer differentiation, induces apoptosis, and predicts disease prognosis. Cancer. 2017 Mar 1;123(5):769-782. doi: 10.1002/cncr.30403. Epub 2016 Nov 2.
Somnay Y, Lubner S, Gill H, Matsumura JB, Chen H. The PARP inhibitor ABT-888 potentiates dacarbazine-induced cell death in carcinoids. Cancer Gene Ther. 2016 Oct;23(10):348-354. doi: 10.1038/cgt.2016.39. Epub 2016 Sep 16.
Jaskula-Sztul R, Xu W, Chen G, Harrison A, Dammalapati A, Nair R, Cheng Y, Gong S, Chen H. Thailandepsin A-loaded and octreotide-functionalized unimolecular micelles for targeted neuroendocrine cancer therapy. Biomaterials. 2016 Jun;91:1-10. doi: 10.1016/j.biomaterials.2016.03.010. Epub 2016 Mar 8.
Chen G, Jaskula-Sztul R, Harrison A, Dammalapati A, Xu W, Cheng Y, Chen H, Gong S. KE108-conjugated unimolecular micelles loaded with a novel HDAC inhibitor thailandepsin-A for targeted neuroendocrine cancer therapy. Biomaterials. 2016 Aug;97:22-33. doi: 10.1016/j.biomaterials.2016.04.029. Epub 2016 Apr 26.