Investigating iASPP as a potential cancer drug target

Abstract

iASPP (inhibitory member of the apoptosis stimulating protein of p53 family) is known to inhibit the important tumor suppressors p53 and p73. Indeed, iASPP is over-expressed in several cancer types and is associated with poor response to chemotherapy and metastasis. It has been demonstrated that iASPP over-expression leads to cancer cell proliferation. Thus, iASPP may be a potential new target for cancer therapy, especially, since iASPP inhibition could potentially initiate apoptosis via p53 or p73 pathways. This is an important advantage because p53 is mutated or deleted in over half of all human tumors. Because of the apparent function of iASPP in inhibiting apoptosis in many cancer types, we chose to investigate whether iASPP would represent a valuable cancer target. In order to evaluate iASPP as a cancer target, we tested whether it could be druggable with small molecules, whether we could develop biological assays to test binding, and whether we could further validate iASPP as a target in our hands using siRNA.