Abstract
Since its identification as a member of the tumour necrosis factor (TNF) family, TRAIL (TNF-related apoptosis-inducing ligand) has emerged as a new avenue in apoptosis-inducing cancer therapies. Its ability to circumvent the chemoresistance of conventional therapeutics and to interact with cancer stem cells (CSCs) self-renewal pathways, amplified its potential as a cancer apoptotic agent. Many recombinant preparations of this death ligand and monoclonal antibodies targeting its death receptors have been tested in monotherapy and combinational clinical trials. Gene therapy is a new approach for cancer treatment which implies viral or non-viral functional transgene induction of apoptosis in cancer cells or repair of the underlying genetic abnormality on a molecular level. The role of this approach in overcoming the traditional barriers of radiation and chemotherapeutics systemic toxicity, risk of recurrence, and metastasis made it a promising platform for cancer treatment. The recent first Food Drug Administration (FDA) approved oncolytic herpes virus for melanoma treatment brings forth the potency of the cancer gene therapy approach in the future. Many gene delivery systems have been studied for intratumoural TRAIL gene delivery alone or in combination with chemotherapeutic agents to produce synergistic cancer cytotoxicity. However, there still remain many obstacles to be conquered for this different gene delivery systems. Nanomedicine on the other hand offers a new frontier for clinical trials and biomedical research. The FDA approved nanodrugs motivates horizon exploration for other nanoscale designed particles’ implications in gene delivery. In this review we aim to highlight the molecular role of TRAIL in apoptosis and interaction with cancer stem cells (CSCs) self-renewal pathways. Finally, we also aim to discuss the different roles of gene delivery systems, mesenchymal cells, and nanotechnology designs in TRAIL gene delivery.
Highlights
The symphony of balance between cell growth and cell death,in order to preserve normal biological functional environment, is maintained through orchestrated processes
In this review we aim to focus on TRAIL, a leading molecule involved in the process of apoptosis and its promising effects as apoptosis inducer for cancer treatment
We aim to highlight the role of different gene delivery systems as alternative approaches to conventional TRAIL-based therapies in cancer
Summary
The symphony of balance between cell growth and cell death,in order to preserve normal biological functional environment, is maintained through orchestrated processes. Among these processes is apoptosis which is programmed cell death [1]. The process of apoptosis itself is still an extremely complicated process in which many molecules and cellular pathways are involved [3]. In this review we aim to focus on TRAIL, a leading molecule involved in the process of apoptosis and its promising effects as apoptosis inducer for cancer treatment. We aim to highlight the role of different gene delivery systems as alternative approaches to conventional TRAIL-based therapies in cancer
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