Molecular targets for selective killing of TRAIL-resistant leukemic cells

Giorgio Zauli, Raffaella Bosco, Paola Secchiero

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines, and shows promising therapeutic activity against solid tumors and lymphomas, in a variety of Phase I and II clinical trials. In contrast, primary leukemias have shown poor susceptibility to TRAIL-mediated cytotoxicity, suggesting the need for sensitizing TRAIL-resistant leukemic cells, by combining soluble recombinant TRAIL either with chemotherapeutic drugs, or with targeted small molecules. Areas covered: This review discusses potential therapeutic applications of combinations able to restore the sensitivity of leukemic cells to either recombinant TRAIL or anti-TRAIL-receptor agonistic antibodies for the treatment of hematological malignancies. Expert opinion: Up-to-date knowledge of the most innovative anti-leukemic therapies including functional screening of specific-sensitizers, enhancing TRAIL-mediated cytotoxicity. Strategies aimed to enhance TRAIL-mediated apoptosis, include the combination of novel sensitizers, functionally identified from libraries of pharmaceutically active, synthetic or naturally derived compounds. Other approaches aim to employ the administration of stem cells engineered to express TRAIL, in the leukemic stem cell niche, and promise to be a successful treatment with reduced specific toxicity.

Original languageEnglish
Pages (from-to)931-942
Number of pages12
JournalExpert Opinion on Therapeutic Targets
Volume15
Issue number8
DOIs
Publication statusPublished - Aug 2011

Keywords

  • Agonistic anti-TRAIL-receptor antibodies
  • Anti-leukemic therapy
  • Stem cells
  • TRAIL

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

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