**6. Conclusion**

A number of preliminary studies sustain the use of TRAs instead of rTRAIL in the treatment of tumour cells protected from TRAIL-induced apoptosis by the expression of cell surface decoy receptors. Although the early clinical trials are promising and well tolerated, it is worth outlining that the utility of both rTRAIL and agonistic anti-TRAIL-Rs antibodies therapies is restricted to patients with TRAIL-sensitive tumours. To restore TRAIL sensitivity in cancer cells novel compounds have been identified and are currently used in combined protocols with TRAIL ligand/TRAs or conventional radio-chemotherapy. Once mechanisms of action/resistance to TRAIL signalling are better understood, approaches to predict patient response and optimize combination regimens may be developed to overcome primary and acquired resistance on the trail to a personalized treatment of cancer.
