An RNAi therapeutic, DFP-10825, for intraperitoneal and intrapleural malignant cancers

Adv Drug Deliv Rev. 2020:154-155:27-36. doi: 10.1016/j.addr.2020.08.002. Epub 2020 Aug 8.

Abstract

RNA interference (RNAi), a potent post-transcriptional gene-silencing action, has received considerable attentions as a novel therapeutic tool to treat intractable cancers. In recent days, we have developed a novel RNAi-based therapeutic formulation, DFP-10825, for the treatment of intractable advanced cancers developed in coelomic cavities. DFP-10825 was composed of chemically synthesized short hairpin RNA (shRNA) against thymidylate synthase (TS), a key enzyme for cancer proliferation, and cationic liposomes, and achieved high therapeutic effect on the mouse models of peritoneally disseminated gastric and ovarian cancers and malignant pleural mesothelioma without severe side effects by intracoelomic direct treatment. We further designed a freeze-dried DFP-10825 formulation for mass industrial production. DFP-10825 is undergoing in pre-clinical phase and goes to clinical trials. This review introduces a DFP-10825 formulation, a potent novel RNAi-based therapeutic maximizing the benefit of RNAi molecule (shRNA).

Keywords: Advanced cancer; Cancer therapy; Cationic liposomes; Freeze-dry; Malignant pleural mesothelioma; Peritoneal dissemination; RNA interference (RNAi); Short hairpin RNA (shRNA); Thymidylate synthase (TS).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Drug Administration Routes
  • Humans
  • Liposomes / administration & dosage*
  • Peritoneal Neoplasms / drug therapy*
  • Pleural Neoplasms / drug therapy*
  • RNA Interference*
  • RNA, Small Interfering / administration & dosage*

Substances

  • Antineoplastic Agents
  • DFP-10825
  • Liposomes
  • RNA, Small Interfering