New somatostatin-drug conjugates for effective targeting pancreatic cancer

E. Ragozin, A. Hesin, A. Bazylevich, H. Tuchinsky, A. Bovina, T. Shekhter Zahavi, M. Oron-Herman, G. Kostenich, M. A. Firer, T. Rubinek, I. Wolf, G. Luboshits, M. Y. Sherman, G. Gellerman

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish
Pages (from-to)3825-3836
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume26
Issue number13
DOIs
StatePublished - 30 Jul 2018

Keywords

  • Pancreatic cancer
  • Peptide conjugate
  • SPPS
  • SSTR
  • Stability profiles
  • Targeted drug delivery

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