New somatostatin-drug conjugates for effective targeting pancreatic cancer

Bioorganic & Medicinal Chemistry
Elena RagozinG Gellerman

Abstract

Pancreatic cancer poorly responds to available drugs, and finding novel approaches to target this cancer type is of high significance. Here, based on a common property of pancreatic cancer cells to express somatostatin receptors (SSTR), we designed drug conjugates with novel somatostatin-derived cyclic peptides (SSTp) with broad selectivity towards SSTR types to facilitate drug targeting of the pancreatic cancer cells specifically. Uptake of our newly designed SSTps was facilitated by SSTRs expressed in the pancreatic cancers, including SSTR2, SSTR3, SSTR4 and SSTR5. Three major drugs were conjugated to our best SSTps that served as delivery vehicles, including Camptothecin (CPT), Combretastatin-4A (COMB) and Azatoxin (AZA). All designed drug conjugates demonstrated penetration to pancreatic cancer cell lines, and significant toxicity towards them. Furthermore, the drug conjugates specifically accumulated in tumors in the animal xenograft model, though some accumulation was also seen in kidney. Overall these findings lay the basis for development of novel drug series that could target the fatal pancreatic cancer.

Citations

Feb 16, 2020·British Journal of Pharmacology·Krishna SriramPaul A Insel
Aug 16, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Christian Bailly
Feb 7, 2021·Journal of Clinical Medicine·Andres Garcia-SampedroPilar Acedo
Apr 29, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Alireza HashemzadehMasoud Mirzaei
Feb 9, 2019·Journal of Medicinal Chemistry·Brian H WhiteMark T Bilodeau

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