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On the TRAIL to successful cancer therapy? Predicting and counteracting resistance against TRAIL-based therapeutics
- Source :
- Oncogene. 32:1341-1350
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
Abstract
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and agonistic antibodies against TRAIL death receptors (DR) kill tumor cells while causing virtually no damage to normal cells. Several novel drugs targeting TRAIL receptors are currently in clinical trials. However, TRAIL resistance is a common obstacle in TRAIL-based therapy and limits the efficiency of these drugs. In this review article we discuss different mechanisms of TRAIL resistance, and how they can be predicted and therapeutically circumvented. In addition, we provide a brief overview of all TRAIL-based clinical trials conducted so far. It is apparent that although the effects of TRAIL therapy are disappointingly modest overall, a small subset of patients responds very well to TRAIL. We argue that the true potential of targeting TRAIL DRs in cancer can only be reached when we find efficient ways to select for those patients that are most likely to benefit from the treatment. To achieve this, it is crucial to identify biomarkers that can help us predict TRAIL sensitivity.
- Subjects :
- Oncology
Cancer Research
medicine.medical_specialty
Cancer therapy
Biology
Models, Biological
Molecular oncology
Article
TRAIL Receptors
TNF-Related Apoptosis-Inducing Ligand
Neoplasms
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
Genetics
medicine
Animals
Humans
Molecular Biology
Cancer
Prognosis
medicine.disease
Review article
Clinical trial
Treatment Outcome
Drug Resistance, Neoplasm
Immunology
Death Receptors
Trail resistance
Signal Transduction
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....819a4d367395f4651c4e8ed5e5e64043