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Sensitization of Therapeutic-Resistant Pancreatic Cancer by Cancer Cell-Specific Drug Delivery


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In the third year of this project, we have completed most of the tasks following the timeline of our Statement of Work, although the COVID-19 pandemic severely affected progress in the second year of the project by interrupting the proposed animal studies. We have partially characterized the two new pancreatic cancer cell lines by verifying their tumorigenicity in athymic mice, and confirmed dose-dependent killing of all the six pancreatic cancer cell lines by HMCD-SIM, all in doses below 12.5 micrometers. In the first test, HMCD-SIM inhibited UN-KPC-960 intrasplenic tumor growth and prolonged 129 mice host survival. Modified experimental protocol will be used in repeated studies to consolidate effect of the conjugate in immune intact mice. In GASP-1 ELISA assays with a wide spectrum of patient samples, it is revealed that substantial amount of GASP-1 was detected in pancreatitis, indicating that the GASP-1 biomarker lacks tumor cell-specificity. We have now confirmed that HMCD-SIM could indeed kill pancreatic cancer cells in vitro and inhibit pancreatic tumor growth in mouse, and completed a manuscript to report this finding. Additionally, with the support of the ongoing DoD PRCRP TTSA Award, we have identified a new entity from pancreatic cancer patient blood samples.



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