Discovery of molecular targets and their validation are crucial to advances in cancer diagnosis,prognosis and therapy.Here I will present an overview of the structure-functional characterization of anti-apoptotic and apoptotic molecules discovered in our laboratory and their significance in cancer biology and therapy.Our analyses included a variety of molecular,biochemical,and biological approaches.TNFAIP8 (earlier reported as SCC-S2) is an NF-κB-and androgen-inducible molecule.Enhanced expression of TNFAIP8 has been correlated with increased tumor growth,in vitro inivasion,and experimental metastasis.Downregulation of TNFAIP8 in tumor cells via siRNA resulted in decreased expression of angiogenic and metastatic molecules,VEGFR2,MMP1,and MMP9 (1).TNFAIP8 appears to be an important prognostic indicator in advanced prostatic adenocarcinomas (2).BLID (earlier reported as BRCC2) is an apoptotic molecule of the Bcl-2 family (3,4).Expression of BLID was found to be decreased or lost in a majority of invasive ductal breast carcinomas (5).In contrast,BLID was found to be expressed in all cases of invasive lobular breast cancers tested.Addition of BLID to the panel of existing biomarkers should improve distinction of these breast tumor subtypes and facilitate treatment strategies.We have also developed liposomal cationic nanoparticles for systemic delivery of antisense oligonucleotides or siRNAs to prostate,breast,and pancreatic tumor xenografis grown in athymic mice (6,7).Preclinical development of the nanoparticles targeting Raf-1,a well known target in cancer therapy,and TNFAIP8 as tumor radiation sensitizers and chemosensitizers will be presented.This work was supported by grants from the National Institutes of Health,Department of Defense,and NeoPharm,Inc.