Inhibitor of apoptosis protein family as diagnostic markers and therapeutic targets of colorectal cancer

Abstract

The apoptosis and antiapoptotic signaling pathways are important for regulating carcinogenesis and cancer progression, and for determining prognosis. Molecules involved in apoptosis represent potential cancer diagnostic markers and therapeutic targets. The inhibitor of apoptosis protein (IAP) family includes several important molecules involved in apoptosis that might represent such targets. Increasing evidence has demonstrated that the IAP family of proteins is integral for antiapoptotic and nuclear factor-κB signal transduction, and enhanced expression of IAPs contributes to colon carcinogenesis and its poor prognosis, as well as to drug resistance of tumors. X-linked IAP, cIAP1, cIAP2, and survivin are prognostic markers of colorectal cancer, and survivin and cIAP2 are also utilized to predict the effect of anticancer treatment in colorectal cancer patients. Novel therapies such as YM155 and LY2181308 targeting survivin, AEG35156 and phenoxodiol targeting X-linked IAP, AT-406 as a Smac mimetic, and survivin peptides are currently being evaluated in clinical trials. This report reviews the involvement of the IAP family in colorectal adenocarcinoma in order to summarize the role of the IAP family members as diagnostic and therapeutic targets, and to provide an overview of the future course of research in this area.

Substituted diaryl diselenides: Cytotoxic and apoptotic effect in human colon adenocarcinoma cells

“…Regardless of the advances in developing new chemotherapy agents, no drug has been able to treat colorectal cancer metastasis with a non-relapsing cure rate. Currently the clinical challenge is to develop new drugs that will have a significant impact on cure rates, by reversing drug resistance, and with minimal toxicity (Miura et al, 2011).…”

Apoptosis as a Therapeutic Target in Cancer and Cancer Stem Cells: Novel Strategies and Futures Perspectives

“…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.…”

A critical role for cellular inhibitor of protein 2 (cIAP2) in colitis-associated colorectal cancer and intestinal homeostasis mediated by the inflammasome and survival pathways

“…34 Furthermore, it is overexpressed in CRC and is a predictive prognostic marker of CRC recurrence after chemotherapy. [35][36][37] As cIAP2 governs prosurvival responses to TNFa and regulates innate immunity pathways, we hypothesized that it is a key regulator of intestinal homeostasis. Here we demonstrate that cIAP2 is a potent promoter of colitisassociated colorectal cancer (CAC) but is also a critical regulator of intestinal tissue repair following injury.…”