**4.2. Use of IAPs into clinic: prognostic and therapeutic values**

The expression and/or function of IAPs are deregulated in many human cancers because of genetic aberrations, an increase in their mRNA or protein expression or the loss of endogenous inhibitors such as Smac. The expression levels of IAPs and their antagonists have been correlated with clinical parameters and cancer prognosis in several retrospective trials. However, these results should be interpreted with caution due to the low numbers of samples studied in some reports and the limitations of currently available reagents for analyzing the expression of IAP proteins in tissue specimens. Therefore, additional studies are required to evaluate the prognostic value of IAPs in human malignancies [10].

The issue of primary or acquired resistance to current chemotherapeutic-based treatments is a major impediment to effective cancer treatment. Although there are many genetic and biochemical alterations that occur in cancer cells, in vitro experiments demonstrate that the up-regulation of IAPs expression increases resistance to chemotherapy and radiation. The fundamental role of the IAPs in apoptosis regulation and their elevated expression in many tumour types suggest that there is value in exploiting the inhibition of IAP expression and function as a direct therapeutic strategy [125].

Novel drugs have been developed and some of them are in current clinical trials. Several strategies have been chosen for anticancer drug development targeting IAP molecules: (1) small-molecule IAP antagonists, (2) antisense oligonucleotides (ASOs), (3) Smac mimetic molecules and others [132]. Small-molecule IAP antagonists and antisense oligonucleotides have garnered the most attention. Also, IAP antagonists have been extensively studied in combination with other cytotoxic agents including anticancer drugs, small-molecule signal transduction inhibitors, proteasome inhibitors and death receptor ligands as well as with radiation therapy.
