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Journey of TRAIL from bench to bedside and its potential role in immuno-oncology

George E. Naoum, Donald J. Buchsbaum, Fady Tawadros, Ammad Farooqi, Waleed O. Arafat
  • George E. Naoum
    Alexandria Comprehensive Cancer Center, Alexandria, Egypt
  • Donald J. Buchsbaum
    Univeristy of Alabama, Birmingham, AL, United States
  • Fady Tawadros
    East Tennessee State University, TN, United States
  • Ammad Farooqi
    Rashid Latif Medical College, Pakistan
  • Waleed O. Arafat
    Alexandria Comprehensive Cancer Center, Alexandria, Egypt; Univeristy of Alabama, Birmingham, AL, USA; University of Alexandria, Faculty of Medicine, Egypt | w.o.arafaat@gmail.com

Abstract

Induction of apoptosis in cancer cells has increasingly been the focus of many therapeutic approaches in oncology field. Since its identification as a TNF family member, TRAIL (TNF-related apoptosis-inducing ligand) paved a new path in apoptosis inducing cancer therapies. Its selective ability to activate extrinsic and intrinsic cell death pathways in cancer cells only, independently from p53 mutations responsible for conventional therapeutics resistance, spotted TRAIL as a potent cancer apoptotic agent. Many recombinant preparations of TRAIL and death receptor targeting monoclonal antibodies have been developed and being tested pre-clinically and clinically both as a single agent and in combinations. Of note, the monoclonal antibodies were not the only type of antibodies developed to target TRAIL receptors. Recent technology has brought forth several single chain variable domains (scFv) designs fused recombinantly to TRAIL as well. Also, it is becoming progressively more understandable that field of nanotechnology has revolutionized cancer diagnosis and therapy. The recent breakthroughs in materials science and protein engineering have helped considerably in strategically loading drugs into nanoparticles or conjugating drugs to their surface. In this review we aim to comprehensively highlight the molecular knowledge of TRAIL in the context of its pathway, receptors and resistance factors. We also aim to review the clinical trials that have been done using TRAIL based therapies and to review various scFv designs, the arsenal of nano-carriers and molecules available to selectively target tumor cells with TRAIL.

Keywords

TRAIL; apoptosis; nanotechnology; single chain antibody.

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Submitted: 2016-12-24 07:07:05
Published: 2017-04-28 12:44:09
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Copyright (c) 2017 George E. Naoum, Donald J. Buchsbaum, Fady Tawadros, Ammad Farooqi, Waleed O. Arafat

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