Targeting TRAIL death receptors.
C N A M Oldenhuis1, J H Stegehuis, A M E Walenkamp
1Department of Medical Oncology, University Medical Center Groningen, The Netherlands.
Current Opinion in Pharmacology
|July 16, 2008
Summary
Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) shows promise as an anticancer agent, particularly for glioblastomas. Combination therapies are being explored to enhance its effectiveness against resistant tumors.
Area of Science:
- Oncology
- Molecular Biology
- Drug Development
Background:
- Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) triggers apoptosis via death receptors.
- Recombinant TRAIL and anti-TRAIL receptor antibodies are potential anticancer agents with low toxicity to normal cells.
Purpose of the Study:
- To review current knowledge on TRAIL-based agents.
- To highlight their potential in treating chemotherapy-resistant glioblastomas.
- To discuss sensitization strategies using bortezomib.
Main Methods:
- Review of existing literature on TRAIL and its analogs.
- Analysis of early-phase clinical trial data.
- Discussion of preclinical combination studies.
Main Results:
- TRAIL-based agents demonstrate limited toxicity and some tumor responses in early clinical trials.
- Glioblastomas are a key focus due to their intrinsic chemotherapy resistance.
- Combination with bortezomib shows potential for sensitizing tumor cells.
Conclusions:
- TRAIL-based therapies are promising anticancer agents in early development.
- Combination strategies are crucial for overcoming resistance, especially in glioblastomas.
- Further research into sensitizing mechanisms, like bortezomib co-administration, is warranted.
Related Concept Videos
01:00Enzyme-linked Receptors
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:27Cytotoxic T Cells-mediated Immune Response
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
02:57Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...
01:30Overview of Cell Death
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...